Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2021 Mar 31;203(6):2747–2760. doi: 10.1007/s00203-021-02300-y

Presence of non-oral bacteria in the oral cavity

Nawel Zaatout 1,
PMCID: PMC8012020  PMID: 33791834

Abstract

A homeostatic balance exists between the resident microbiota in the oral cavity and the host. Perturbations of the oral microbiota under particular conditions can contribute to the growth of non-oral pathogens that are hard to kill because of their higher resistance to antimicrobials, raising the probability of treatment failure and reinfection. The presence of these bacteria in the oral cavity has been proven to be associated with several oral diseases such as periodontitis, caries, and gingivitis, and systemic diseases of importance in clinical medicine such as cystic fibrosis, HIV, and rheumatoid arthritis. However, it is still controversial whether these species are merely transient members or unique to the oral cavity. Mutualistic and antagonistic interactions between the oral microbiota and non-oral pathogens can also occur, though the mechanisms used by these bacteria are not clear. Therefore, this review presents an overview of the current knowledge about the presence of non-oral bacteria in the oral cavity, their relationship with systemic and oral diseases, and their interactions with oral bacteria.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00203-021-02300-y.

Keywords: Oral microbiota, Non-oral bacteria, Periodontitis, Systemic diseases

Introduction

The oral cavity is a complex and dynamic environment and is the primary gateway to the human body (Zarco et al. 2012; Craig et al. 2018). Various studies have identified over 1000 species from the oral cavity that forms the oral microbiota (Mahasneh et al. 2017; Gao et al. 2018). However, only a tiny fraction is causing oral infections such as dental caries and periodontitis (Kreth and Merritt 2009; Dewhirst et al. 2010). An imbalance of microbial flora contributes to the growth of various clinically important pathogens, that are generally considered ‘‘non-oral’’ bacteria, such as Gram-negative enteric rods (GNRs), enterococci, and staphylococci (Al-Ahmad et al. 2009; Van Winkelhoff et al. 2016). Non-oral bacteria are non-resident, super-infectious microorganisms that are not generally considered a common part of the oral microbiota. Their eradication from the dental biofilms seems to be more challenging due to their higher resistance to antimicrobials, raising the probability of treatment failure and reinfection (Souto et al. 2006). There has been a great deal of confusion in the literature regarding their natural reservoir and their ability to colonize the oral cavity. Previous studies have revealed that they may occur in high numbers and shift from transitory species to colonizers of the oral cavity in immunocompromised individuals (Simões-Silva et al. 2018; Arirachakaran et al. 2019). However, some studies have shown that they can colonize healthy subjects too (Ranganathan et al. 2017; Chinnasamy et al. 2019). Moreover, systemic colonization and infections associated with non-oral bacteria isolated from the oral cavity have been revealed (Arirachakaran et al. 2019; Ghapanchi et al. 2019), making the oral cavity an extra-hospital reservoir (Kearney et al. 2020).

Currently, there are a limited understanding and limited information regarding the pathogenesis of non-oral bacteria in the oral cavity. To the best of our knowledge, there are no reviews on the role of non-oral bacteria in the oral cavity and their relationship with the oral microbiota. Therefore, this review examines the current knowledge about the most extensively studied non-oral bacteria in the oral cavity and also provides an overview of the interactions between the oral microbiota and non-oral bacteria.

Non-oral bacteria in the oral cavity: transitory species or colonizers?

Non-oral bacteria are commonly found in other parts of the human body (nares or gut). They can accidentally be introduced into the mouth by food, water, contact with animals, mouthing and chewing items, etc. Nevertheless, nowadays, there is a controversy about whether the oral cavity is an entry point or an important reservoir for this group of bacteria and whether they are merely transient or unique to this niche (Zuanazzi et al. 2010; Vieira Colombo et al. 2016).

There has been strong evidence that they might colonize the oral ecosystem (Souto and Colombo 2008a; Gonçalves et al. 2007a; Da Silva-Boghossian et al. 2011). Patients positive with certain subgingival non-oral species, most notably Acinetobacter baumannii and Pseudomonas aeruginosa, are reported to show a higher percentage of periodontal sites with suppuration on probing (Silva-Boghossian et al. 2013), greater periodontal attachment loss (Da Silva-Boghossian et al. 2013; Van Winkelhoff et al. 2016) and much more aggressive forms of periodontitis. Furthermore, some of these bacteria isolated from the oral cavity, such as enterococci, were found to be genetically different from isolates from other parts of the human body (Vidana et al. 2011), which could potentially lead to another understanding of the ecosystem of the oral cavity.

The disturbance of the “equilibrium” (due to medical treatments, biological changes, or inadequate hygiene) between commensal bacteria and the host immune system could be the reason for the shift of non-oral bacteria from transitory species to colonizers (Handal et al. 2003; Dahlen 2009; Tada and Hanada 2010), and could enhance the subsequent morbid microbial communities in the compromised host (Botero et al. 2007a; Vieira Colombo et al. 2016). However, in normal oral health conditions, one should not expect these microorganisms to overcome in proportions the very well adapted oral species (Van Winkelhoff et al. 2016).

The most extensively studied species in the oral cavity are species of Enterobacteriaceae, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Acinetobacter baumannii. The presence of unique and specific virulence factors can help in distinguishing between these different species.

Enterobacteriaceae

Enterobacteriaceae is a family of Gram-negative rods that have stood out in the healthcare environment due to the variety of severe infections that they can cause and their resistance to antibiotics (Leão-Vasconcelos et al. 2015). Their presence in the oral ecosystem is perhaps due to the ingestion of contaminated drinking water, food or poor personal hygiene (Barbosa et al. 2001; Gonçalves et al. 2007b). The prevalence of GNRs in the oral environment is extremely variable, and it is still not clear whether they are colonizing or merely transient bacteria. This is probably due to the use of single-sample techniques that do not allow the differentiation between transient presence and persistent presence (Martinez-Pabon et al. 2010). However, it has been shown that the prolonged transportation time of the samples may encourage the multiplication of GNRs, leading to higher positive results (Ali et al. 1996).

Moreover, numerous studies on GNRs pathogenesis in the oral ecosystem have shown that (1) they can persist within the subgingival environment after periodontal debridement and surgery (Slots et al. 1991), (2) they are implicated as key pathogens in cases of refractory periodontitis (Edwardsson et al. 1999), (3) they are detected at greater frequency and in higher proportions in patients with failing implants (Listgarten et al. 1999) and (4) they are usually associated with oral mucosal infections in immune-compromised patients. In these patients, oral mucosal infections may spread to the respiratory system and trigger life-threatening infections (Scannapecio et al. 2009; Tada and Hanada 2010). Furthermore, their virulence factors are conferred through several properties that give the ability to adhere and invade the host’s tissues (Kazemian et al. 2017). Such as the release of enterotoxins and endotoxins, elaboration of extracellular leukotoxins, degradation of immunoglobulins IgG and IgA, suppression of lymphocyte proliferation and elaboration of collagenolytic and other proteolytic enzymes (Barbosa et al. 2001). Nevertheless, the GNRs are rarely identified at the species level, and they are referred to as “enterics” (Martinez-Pabón et al. 2010). However, the group is made up of a wide variety of bacterial species, which are incongruent in pathogenicity, virulence and antibiotic susceptibility (Arirachakaran et al. 2019). At the species level, some authors have found that some Gram-negative rods can dominate among oral species in some cases, like Pereira et al. (2013) who found that K. pneumoniae is the dominant bacterial species in cases wearing removable maxillary prosthesis with and without denture stomatitis lesions. Also, according to Zhu et al. (2008), there exists an important correlation between the presence of K. pneumoniae in the oral cavity and the risk of pneumonia by aspiration of these bacteria in people suffering from a stroke.

Moreover, its ability to degrade elastin (which is perceived to be a marker of P. aeruginosa in the aetiology of lower respiratory tract infections (Beatty et al. 2005)) could contribute to its virulence (Goncalve et al. 2007). Thurnheer and Belibasakis (2015) observed that when Escherichia coli are given the appropriate nutritional and environmental conditions, they can endure and even dominate among oral species in a polymicrobial biofilm. However, Back-Brito et al. (2011) have found considerably higher numbers of enteric bacteria in the oral cavities of HIV-positive patients, and Enterobacter cloacae were the most frequently isolated species (Table 1, the search strategy is in the supplementary file, Table S1). Interestingly, it was found that the presence of Candida albicans in the oral cavity can increase the growth and the swarming activity of Proteus mirabilis (Kart et al. 2020).

Table 1.

Summary of studies in which non-oral bacteria have been isolated in patients with systemic or oral diseases

Diseases Non-oral bacteria Study group/study type Age Prevalence of non-oral bacteria (%) Specimen (s) collected Country Referencesa
Periodontitis

GNRsb

S. aureus

PGc: 535 patients

A cross-sectional study

19–70 years

34.9%

6.2%

Periodontal pockets Sweden Dahlen and Wikström (1995)

GNRs

Pseudomonas

PG: 80 patients

A cross-sectional study

17–58 years

18.8%

10.0%

Periodontal pockets Brazil Barbosa et al. (2001)
GNRs

PG: 80 patients

A cross-sectional study

35–60 years 20% Periodontal pockets Brazil Gonçalves et al. (2007b)
H. pylori

PG: 169 patients

CGd: 56 healthy subjects

A cross-sectional study

41 ± 14

34.3 ± 12

50% (PG)

11.4 (CG)

Subgingival plaque samples Brazil Souto and Colombo (2008b)
E. faecalis

PG: 169 patients

CG: 56 healthy subjects

A cross-sectional study

41 ± 14

34.3 ± 12

47.8% (PG)

17.1% (CG)

Subgingival plaque samples Brazil Souto and Colombo (2008a)
S. aureus

PG: 106 patients

A cross-sectional study

 ≥ 18 years 24.6% Subgingival plaque samples Switzerland Fritschi et al. (2008)
Staphylococcus spp. PG: 82 patients 18–70 years 42.7% Subgingival plaque samples Argentina Cuesta et al. (2010)
GNRs

PG: 63 patients

CG: 45 healthy subjects

A prospective cohort

33.29 ± 7.79

43.95 ± 8.97

16.7% (PG)

9.3% (CG)

Periodontal pockets Colombia Martínez-Pabón et al. (2010)
E. faecalis

PG: 32 patients

A prospective longitudinal study

≥ 18 years 40.6% Root canal samples China Zhu et al. (2010)

P. aeruginosa

Acinetobacter spp.

PG: 169 patients

CG: 55 healthy subjects

A cross-sectional study

40.2 ± 14

31.1 ± 11

52.2% (PG), 11.4% (CP)

56.5% (PG), 31.4% (CP)

Periodontal pockets Brazil Souto et al. (2014)
GNRs

PG: 102 patients

A cross-sectional study

48 ± 13.2 42.9% Subgingival plaque samples Netherlands Van Winkelhoff et al. (2016)

GNRs

P. aeruginosa

PG: 42 patients

CG: 42 healthy subjects

Case–control study

43.48 ± 12.46

29.36 ± 8.99

83.3% (PG), 71.4% (CG)

30.9% (PG), 28.5% (CG)

Subgingival plaque samples India Ranganathan et al. (2017)
Dental caries

E. faecalis,

E. faecium

PG: 34 caries active subjects

CG: 28 caries free subjects

A cross-sectional study

4–12 years

46.9% (PG), 7% (CG)

9.5% (PG), 7% (CG)

Saliva Tunisia Kouidhi et al. (2011)
S. aureus

PG: 105 healthy subjects

A cross-sectional study

45.84 ± 15.82 20% Dental abscess, caries and saliva Tunisia Merghni et al. (2014)
Root canal infection E. faecalis

PG: 100 patients

CG: 100 healthy subjects

A cross-sectional study

32–72 years

11% (PG)

1% (CG)

Oral rinse samples USA Sedgley et al. (2004)
E. faecalis

PG: 41 patients

A cross-sectional study

42.6 ± 15.3 10%

Oral rinse

samples

USA Sedgley et al. (2006)

E. faecalis

Staphylococcus spp

Pseudomonas spp

A. baumannii

PG: 50 patients

A cross-sectional study

23–76 years

16%

2%

2%

2%

Root canal samples Sweden Vidana et al. (2011)
Cystic fibrosis (CF) P. aeruginosa

PG: 31 patients

CG: 31 healthy subjects

5–29 years

45.16% (PG)

3.22 (CG)

Oral cavity samples Canada Komiyama et al. (1985)
P. aeruginosa

PG: 5 patients

CG: 5 healthy subjects

Case–control study

16–34 years

12–27 years

100% (PG)

0% (CG)

Sputum samples France Rivas Caldas et al. (2015)
Orofacial granulomatosis and Crohn’s disease S. aureus

PG: 450 patients

A prospective cohort

13–29 years 0.8% Oral rinse samples UK Gibson et al. (2000)
Oral cancer

Staphylococcus spp.

P. aeruginosa

PG: 46 patients

CG: 37 healthy subjects

A cross-sectional study

67.4 ± 10.3

71.3 ± 9.9

43.7% (PG), 56.3% (CG)

57.1% (PG), 42.9% (CG)

Saliva and surgical scar Japan Yamashita et al. (2013)

S. aureus

E. coli

S. epidermidis

PG: 40 patients

A cross-sectional study

/

23.2%

15.62%

12.5%

Swabs over the cancerous lesion India Panghal et al. (2011)
HIV

S. aureus

P. aeruginosa

K. pneumoniae

PG: 14 periodontitis patients

A cross-sectional study

25–50 years

6.8%

6.7%

6.7%

Subgingival plaque samples USA Rams et al. (1991)
GNRs

PG: 31 periodontitis patients

CG: 32 healthy subjects

A cross-sectional study

37.3 ± 9.3

22.8 ± 8.5

74.2% (PG)

18.8% (CG)

Subgingival plaque samples Colombia Botero et al. (2007b)

S. aureus

S. epidermidis

E. cloacae

PG: 45 HIV subjects

CG: 45 healthy subjects

A cross-sectional study

22–66 years

23–66 years

92.4% (PG), 54% (CG)

47% (PG),61.8% (CG)

22.3% (PG), 18.1% (CG)

Oral rinse samples Brazil Back-Brito et al. (2011)

P. mirabilis

S. aureus

P. aeruginosa

PG: 605 HIV subjects

A cross-sectional study

1–60 years

16.4%

11.3%

8.6%

Oral lesions samples Uganda Agwu et al. (2015)

Coliforms

Pseudomonas spp.

S. aureus

Enterococci

PG: 221 HIV patients

PG: 30 healthy subjects

A cross-sectional study

8–69 years

27–47 years

15% (PG), 3% (CG)

11% (PG), 7% (CG)

14%(PG), 17% (CG)

2% (PG), 0% (CG)

Dorsum of the Tongue Thailand Arirachakaran et al. (2016)

Pseudomonas spp.

Enterobacter spp.

Klebsiella spp.

Aeromonas spp.

PG: 255 Thai HIV-positive

adults on Highly active anti-retrovirus therapy (HAART)

CG: 30 healthy subjetcs

A cross-sectional study

/

9.01% (PG), 3.33% (CG)

4.31% (PG), 6.66% (CG)

5.49% (PG), 23.3% (CG)

3.92% (PG), 6.66% (CG)

Dorsum of the tongue, gingiva, periodontal pocket Thailand Arirachakaran et al. (2019)
Rheumatoid arthritis S. aureus

PG: 111 patients

CG: 83 healthy subjects

A cross-sectional study

58.7 ± 11.64

55.9 ± 12.91

12.5% (PG)

3.6% (CG)

Oropharynx samples USA Jacobson et al. (1997)

S. epidermidis

S. aureus

PG: 25 patients

CG: 50 healthy subjects

A cross-sectional study

21–82 years

18–54 years

84% (PG), 88% (CG)

56% (PG), 24% (CG)

Oral rinse samples and tongue swabs UK Jackson et al. (1999)
Parkinson’s disease GNRs

PG: 50 patients

A cross-sectional study

71–90 years 32% A swab around the tonsillar area and soft palate UK Gosney et al. (2003)
Burns, skin, grafting and lacerations Staphylococcus spp.

PG: 28 patients

A cross-sectional study

14–84 years 53.57% Supragingival plaque and oral rinse samples UK Smith et al. (2003a)
Heart disease

Staphylococcus spp.

Pseudomonas spp.

Acinetobacter spp.

PG: 30 patients undergoing myocardium revascularisation surgery (Pre-surgery results)

A prospective cohort

62.66 ± 4.01

85.7%

83.8%

53.3%

Saliva and subgingival plaque samples Brazil Zuanazzi et al. (2010)
Dyspepsia H. pylori

PG: 30 patients

CG: 20 healthy subjects

A cross-sectional study

46.2 ± 11.44

44.5 ± 11.36

60% (PG)

15% (CG)

Subgingival plaque samples India Agarwal and Jithendra (2012)
Endocarditis E. faecalis

PG:1 patient with arrhythmia

A case report

67 years old 100% (PG) A swab from Gingival mucosa Japan Okui et al. (2015)
Head and neck cancer Gram-negative bacilli S. aureus

PG: 110 patients

CG:50 healthy subjects

A prospective case–control

20–80 years

63.6% (PG), 2% (CG)

8% (PG), 0% (CG)

Saliva India Soni et al. (2017)
Chronic kidney disease (CKD) S. epidermidis

PG: 21 end-stage CKD adult patients

CG:14 healthy subjects

A cross-sectional study

46.8 ± 9.7

42.2 ± 14.5

89.5% (PG)

92.3% (CG)

Saliva Portugal Simões-Silva et al. (2018)
P. aeruginosa

PG: 1 HIV-positive subject

A case report

6 years old 100% Biopsy of the gingival tissue Brazil Souza et al. (2018)
Chronic nail biting GNRs

PG: 60 Nail biting subjects

CG: 30 healthy subjects

A cross-sectional study

11 ± 3.0

12 ± 3.5

75% (PG)

40% (CG)

Saliva India Chinnasamy et al. (2019)
Liver transplantation E. faecalis

PG: 100 patients

CG: 100 healthy subjects

A cross-sectional study

10–67 years

10–77 years

2% (PG)

1% (CG)

Saliva Iran Ghapanchi et al. (2019)

aInclusion and exclusion criteria and search strategy are in the supplementary file

bGNRs Gram-negative rods

cPG Patients group

dCG Control group

Staphylococcus aureus

Although the anterior nares are considered the primary ecological niche for Staphylococcus (Kearney et al. 2020), their presence in the oral cavity is unquestionable (Soni et al. 2017) but controversial (Smith et al. 2001), as it is not clear whether they play a part in the ecology of the healthy oral flora or not (Smith et al. 2003a; Blomqvist et al. 2015).

However, many authors have indicated that the oral cavity functions as a potential reservoir for S. aureus infections in immunosuppressed patients (Agwu et al. 2015; Merghni et al. 2015) (Table 1) and might cause some oral diseases such as periodontitis and dental caries (Fritschi et al. 2008; Merghni et al. 2014); and systemic diseases such as heart disease, chronic kidney disease, orofacial granulomatosis and Crohn’s disease (Gibson et al. 2000; Zuanazzi et al. 2010; Simões-Silva et al. 2018). Oral S. aureus has also been recognized as an aetiological factor of infective endocarditis (Carmona et al. 2002).

Persson and Renvert (2014) found that S. aureus is present at higher amounts in biofilms obtained from implants with peri-implantitis than peri-implant healthy subjects. Other studies have revealed that S. aureus was found at higher levels in the oral cavity and with greater prevalence in periodontitis than non-periodontitis subjects (Souto et al. 2006; Persson et al. 2008), while Fritschi et al. (2008) found higher levels of S. aureus in aggressive than chronic periodontitis subjects. Consequently, S. aureus was pointed out as a contributor to the microbial profiles that could differentiate between aggressive and chronic forms of the disease. Moreover, S. aureus was found at higher levels in the oral cavity of patients with rheumatoid arthritis than healthy controls (Jackson et al. 1999) and was the most frequently isolated species in the oral cavities of HIV-positive patients (Back-Brito et al. 2011). The ability of S. aureus to cause such a diverse array of problems is due to its arsenal of virulence factors that are coordinately expressed during different stages of infection, such as superantigens, toxins such as β-toxin, matrix-binding surface adhesins, biofilm formation and tissue-degrading enzymes such as proteases, lipases, nucleases, and collagenases (Lowy 1998; Merghni et al. 2014; Lima et al. 2019).

Enterococcus faecalis

E. faecalis is not yet considered a normal inhabitant of the oral cavity (Kouidhi et al. 2011) but has been isolated from various oral conditions, including periodontitis and dental caries (Zhu et al. 2010; Kouidhi et al. 2011) (Table 1). It is perceived to be the predominant infectious agent associated with primary and secondary endodontic infections (Vidana et al. 2011) because of its ability to reside within different layers of the oral biofilm, and co-aggregate with different saliva bacteria, which leads to failure of endodontic therapy (Al-Ahmad et al. 2010).

Moreover, it has been found that E. faecalis can preserve viability in root canals ex vivo for at least 12 months (Sedgley et al. 2005); this is perhaps due to its ability to form biofilms (Al-Ahmad et al. 2009, 2014) or colonize multi-species supragingival biofilms (Thurnheer and Belibasakis 2015). Furthermore, coexistence between enterococci and C. albicans has been observed in immunocompromised patients (Almståhl et al. 2001, 2008).

The origin of these opportunistic bacteria in the oral cavity is not yet clear. Wang et al. (2011) demonstrated that the prevalence of E. faecalis in the root canal system had been correlated with its occurrence in saliva. Meanwhile, some authors suggested nosocomial transmission from environmental surfaces in dental surgeries due to the robust nature of the microorganisms (Vidana et al. 2011; Lins et al. 2019), while others proposed foodborne transmission (Zehnder and Guggenheim 2009). However, Vidana et al. (2011) examined the genetic relationship between E. faecalis from root canals and isolates from different host sources and found that isolates from the root canals were not related to those from the typical gastrointestinal microflora, and none of these patients was recorded to have enterococci in their saliva. Likewise, Cole et al. (1999) did not find any members of this species in the saliva probes from 10 infants. Further investigations are needed to minimize the dissemination of virulent and multidrug-resistant clones to the oral cavity. In addition to their role in oral diseases, subsequent systemic colonization and infection associated with an oral source of enterococci have been found; Okui et al. (2015) reported a case of infective endocarditis of oral origin caused by E. faecalis, while Arirachakaran et al. (2016) isolated oral enterococci from HIV patients.

The most studied virulence factors of E. faecalis include biofilms, aggregation substance, gelatinase, lipoteichoic acid, the cytolysin toxin, surface adhesins, extracellular superoxide, sex pheromones, and hyaluronidase. Each of these factors might be associated with many phases of endodontic infections, periapical inflammation, and systemic diseases (Kayaoglu and Ørstavik 2004; Anderson et al. 2016; Komiyama et al. 2016).

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative bacillus that most often affects the lower respiratory system and is associated with nosocomial infections (Watanabe et al. 2009). It can be part of the transient oral microbiota but seldom colonize the oral cavity, which is perhaps due to its strong aerobic character (Arirachakaran et al. 2019). However, studies using molecular biology methods have revealed that its presence in the oral cavity is underestimated and it is much higher in complex biofilms (Wade 2013; Souza et al. 2018).

Moreover, these species have many virulence properties such as the ability to adhere to and form biofilms on tissues and abiotic surfaces (Smith and Iglewski 2003b), along with their ability to produce and secrete extracellular enzymes and toxins (Smith and Iglewski 2003b; Pihl et al. 2010) as well as the expression of multiple antimicrobial resistance elements (Livermore 2002). P. aeruginosa has also been identified in the periodontal pockets of immunocompromised subjects (Nakou et al. 1997) and might be an important pathogen in periodontitis and gingivitis (Persson et al. 2008; Vieira Colombo et al. 2016) (Table 1).

Moreover, they are perceived to be the main pathogen in chronic obstructive pulmonary disease and biofilms on vehicles at intubation (Ewan et al. 2015). Their passage into the lungs may occur by passive aspiration of the bacterial microbiota released in saliva or eased by medical devices such as bronchoscopes and endotracheal tubes (Scannapieco et al. 2009). Lately, oral P. aeruginosa has been associated with oral squamous cell carcinoma (Al-Hebshi et al. 2017) and chronic kidney disease (Simões-Silva et al. 2018). Additionally, focal necrotizing lesions have been found in the oral mucosa of HIV-positive patients, which are different from periodontal disease patterns and are related to the presence of oral P. aeruginosa (Souza et al. 2018).

Acinetobacter baumannii

A. baumannii is a Gram-negative bacillus often found in the hospital environment. It is among the red list group of ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter species) announced as a critical priority pathogen by World Health Organization (WHO) (WHO 2017).

There are not many reports on the incidence of A. baumannii in the oral cavity or its association with oral diseases; though some studies have found that it is significantly associated with suppuration in chronic periodontitis patients, aggressive periodontitis and root canal infections (Da Silva-Boghossian et al. 2013; Vidana et al. 2011; Souto et al. 2014), especially in patients with human immunodeficiency virus (Gonçalves et al. 2007a). Also, the likelihood of a subject being refractory to periodontal treatment increases when A. baumannii is present (Colombo et al. 1998). Furthermore, it is a major pathogen in ventilator-associated pneumonia, which is a massive problem in hospitals, particularly in intensive care units (Lee et al. 2012; Martinez-Lamas et al. 2014), and was isolated from patients suffering from heart disease (Zuanazzi et al. 2010).

Major virulence factors that were studied in A. baumannii isolated from the oral cavity are lipocalins production, biofilm formation, siderophore-mediated iron-acquisition system, outer membrane protein A, desiccation resistance and the ability to bypass the glucose metabolism, which can be considered as one of the key factors that help this bacteria survive in a nutrition-deficient environment (Richards et al. 2015; Priyadharsini et al. 2018).

Interactions between the oral microbiota and non-oral bacteria

In the oral cavity, where resources are limited, collaborations between species are needed to survive and endure. Some studies have shown the physical and metabolic interactions that exist between members of the oral microbiota and non-oral species; they can be mutualistic interspecies interactions (coaggregation) to form biofilms or antagonistic interactions to prevent the integration of a non indigenous bacterial species (Table 2). However, the biological mechanisms underlying these interactions are not yet clear.

Table 2.

Interactions between non-oral bacteria and oral microorganisms in the oral cavity

Non-oral bacteria Oral bacteria Type of interaction Referencesa
P. aeruginosa A. viscosus Coaggregation Komiyama and Gibbons (1984)
P. aeruginosa

S. sanguis, S. mitis

A. naeslundii

Komiyama et al. (1987)
S. aureus F. nucleatum Tawara et al.(1996)
H. pylori Fusobacterium Andersen et al. (1998)
GNRs P. gingivalis, T. forsythia Socransky et al. (1998)
S. aureus

A. Naeslundii

A. viscosus

P. gingivalis

Kamaguchi et al. (2003)
Weissella cibaria F. nucleatum Kang et al. (2005)
E. faecalis F. nucleatum Johnson et al. (2006)
GNRs P. gingivalis Ardila et al. (2011)
A. baumannii T. forsythia, P. gingivalis, T.denticola Da Silva-Boghossian et al. (2011)
P. aeruginosa
GNRs A. actinomycetemcomitans Ardila et al. (2012)
S. aureus F. nucleatum, P. gingivalis Lima et al. (2019)
S. aureus Viridans group streptococci Uehara et al. (2001)
H. pylori

S. oralis

S. mutans

S. sobrinus

A. naeslundii

P. intermedia

P. nigrescens

Antagonistic relationship Okuda et al. (2003)

P. aeruginosa

A. baumannii

S. sanguinis Watanabe et al. (2009)

E. faecalis

S. aureus

A. actinomycetemcomitans Da Silva-Boghossian et al. (2011)
P. aeruginosa

S. parasanguinis

S. sanguinis

S. gordonii

Scoffield and Wu. (2015)
E. faecalis S. oris, S. mutans Thurnheer and Belibasakis (2015)

Coaggregation is defined as cell-to-cell adhesion in which cells of a species adhere more or less specifically to different species (Kolenbrande 2000). This mechanism is involved in the establishment and maintenance of biofilms (Kolenbrander et al. 2010). For instance, in periodontitis patients, an association was found between GNRs and Porphyromonas gingivalis with Tannerella forsythia; both members of the “red complex” bacterial species are associated with severe forms of periodontitis (Socransky et al. 1998). Ardila et al. (2011, 2012) also reported a positive subgingival correlation between GNRs and P. gingivalis, and between GNRs and Aggregatibacter actinomycetemcomitans. Likewise, E. faecalis strains coaggregated with Fusobacterium nucleatum (Johnson et al. 2006), which was able to co-aggregate with Helicobacter pylori (Andersen et al. 1998) and S. aureus (Tawara et al. 1996; Lima et al. 2019). Fusobacterium is considered a key microorganism in the process of coaggregation among different genera and might work as a bridge between early and late colonizers (Andersen et al. 1998; Souto and Colombo 2008b). Previous studies have demonstrated that F. nucleatum utilizes the surface protein RadD to bind and form a dual-species biofilm with other oral species (Park et al. 2016; Lima et al. 2017). Moreover, Da Silva-Boghossian et al. (2011) demonstrated that P. aeruginosa seemed to have synergism with A. actinomycetemcomitans, raising the risk of periodontal disease. Nonetheless, in the same study, the presence of E. faecalis, or S. aureus in association with A. actinomycetemcomitans decreased the risk of periodontal disease. However, other studies have revealed that S. aureus and E. faecalis were detected at higher levels and with greater prevalence in periodontitis than the non-periodontitis subjects (Fritschi et al. 2008; Persson et al. 2008). The differences in methods of detection and ecological variables may account for the data variability amongst these studies.

Antagonistic relationships are also detected in such intricate microbial communities. Nutritional competition between two early colonizers of the oral cavity and E. faecalis was observed. It was shown that the presence of E. faecalis in the oral plaque causes a significant reduction in the numbers of Streptococcus oralis and Streptococcus mutans (Thurnheer and Belibasakis 2015), which is in line with other studies demonstrating that E. faecalis dominates numerically over S. mutans in dual-species biofilms (Deng et al. 2009; Li et al. 2014).

Moreover, Okuda et al. (2003) found that Streptococcus oralis, Actinomyces naeslundii, Streptococcus mutans, Prevotella intermedia, Prevotella nigrescens, and Streptococcus sobrinus, produce bacteriocin-like inhibitory proteins against H. pylori. The fact that subjects with good oral hygiene harbor less H. pylori in their mouths could also be due to the inhibitory activity of the early colonizers of dental biofilms, such as oral streptococci, over that species (Anderson et al. 1998). Likewise, Watanabe et al. (2009) demonstrated that a substance called the ‘‘new-antipseudomonal substance’’ derived from Streptococcus sanguinis could have bactericidal activity against A. baumannii and P. aeruginosa. Nevertheless, these complex and dynamic interactions remain unknown. More profound studies focusing mainly on quorum sensing are needed to understand how non-oral bacteria regulate their genes and coordinate cooperative behaviors in the presence of oral bacteria.

Conclusion and future outlooks

The complex and dynamic interactions in the oral ecosystem between oral and non-oral bacteria are far from being wholly unraveled, and the pathogenetic mechanisms used by these microorganisms are still unclear. Nevertheless, it is clear that non-oral bacteria are not passive bystanders and could play an essential role in oral and systemic diseases. Some non-oral bacteria, such as those covered by this review, are becoming major microbes in the oral cavity and they are increasingly isolated from healthy subjects.

This review highlighted the possible role, versatility, and pathogenic potential of non-oral bacteria in the oral cavity. However, some studies that were used displayed some limitations. Most of the studies available on this subject were cross-sectional studies. Longitudinal studies are also needed to track the presence of these bacteria over an extended period. Assessing quantitatively, the presence of non-oral bacteria is of utmost importance and not just counting on presence/absence. Furthermore, molecular biology methods are also needed to see whether non-oral bacteria are genetically different from isolates from other parts of the human body.

Despite the limitations, the presence of non-oral bacteria in the oral cavity is clearly worrisome. It needs more attention to broaden our understanding of the oral ecosystem and develop novel and more adequate preventive and therapeutic approaches, as well as diagnostic applications so that we can control the spread of non-oral bacteria and render them incapable of damaging the host.

Supplementary Information

Below is the link to the electronic supplementary material.

Author’s contributions

NZ conceptualized and wrote this article.

Funding

This work received no external funding.

Declarations

Conflict of interest

The author declares no conflict of interest.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. Agarwal S, Jithendra KD. Presence of Helicobacter pylori in subgingival plaque of periodontitis patients with and without dyspepsia, detected by polymerase chain reaction and culture. J Indian Soc Periodontol. 2012;16(3):398–403. doi: 10.4103/0972-124X.100919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agwu E, Ihongbe JC, Ezeonwumelu JO, Lodhi MM. Baseline burden and antimicrobial susceptibility of pathogenic bacteria recovered from oral lesions of patients with HIV/AIDS in South-Western Uganda. Oral Sci Int. 2015;12(2):59–66. doi: 10.1016/S1348-8643(15)00018-X. [DOI] [Google Scholar]
  3. Al-Ahmad A, Müller N, Müller N, Wiedmann-Al-Ahmad M, Hellwig E. Endodontic and salivary isolates of Enterococcus faecalis integrate into biofilm from human salivary bacteria cultivated in vitro. J Endod. 2009;35(7):986–991. doi: 10.1016/j.joen.2009.04.013. [DOI] [PubMed] [Google Scholar]
  4. Al-Ahmad A, Ameen H, Pelz K, Karygianni L, Wittmer A, Hellwig E. Antibiotic resistance and capacity for biofilm formation of different bacteria isolated from endodontic infections associated with root-filled teeth. J Endod. 2014;40(2):223–230. doi: 10.1016/j.joen.2013.07.023. [DOI] [PubMed] [Google Scholar]
  5. Al-Hebshi NN, Nasher AT, Maryoud MY, Homeida HE, Chen T, Idris AM, Johnson NW. Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci Rep. 2017;7(1):1834. doi: 10.1038/s41598-017-02079-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ali RW, Velcescu C, Jivanescu MC, Lofthus B, Skaug N. Prevalence of 6 putative periodontal pathogens in subgingival plaque samples from Romanian adult periodontitis patients. J Clin Periodontol. 1996;23(2):133–139. doi: 10.1111/j.1600-051x.1996.tb00546.x. [DOI] [PubMed] [Google Scholar]
  7. Almståhl A, Wikström M, Kroneld U. Microflora in oral ecosystems in primary Sjögren's syndrome. J Rheumatol. 2001;28(5):1007–1013. [PubMed] [Google Scholar]
  8. Almståhl A, Wikström M, Fagerberg-Mohlin B. Microflora in oral ecosystems in subjects with radiation-induced hyposalivation. Oral Dis. 2008;14(6):541–549. doi: 10.1111/j.1601-0825.2007.01416.x. [DOI] [PubMed] [Google Scholar]
  9. Andersen RN, Ganeshkumar N, Kolenbrander PE. Helicobacter pylori adheres selectively to Fusobacterium spp. Oral Microbiol Immunol. 1998;13(1):51–54. doi: 10.1111/j.1399-302x.1998.tb00751.x. [DOI] [PubMed] [Google Scholar]
  10. Anderson AC, Jonas D, Huber I. Enterococcus faecalis from food, clinical specimens, and oral sites: prevalence of virulence factors in association with biofilm formation. Front Microbiol. 2016;6:1534. doi: 10.3389/fmicb.2015.01534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ardila CM, López MA, Guzmán IC. Positive correlations between presence of gram negative enteric rods and Porphyromonas gingivalis in subgingival plaque. Acta Odontol Latinoam. 2011;24(1):15–19. [PubMed] [Google Scholar]
  12. Ardila CM, Alzate J, Guzmán IC. Relationship between Gram negative enteric rods, Aggregatibacter actinomycetemcomitans, and clinical parameters in periodontal disease. J Indian Soc Periodontol. 2012;16:65–69. doi: 10.4103/0972-124X.94607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Arirachakaran P, Poovorawan Y, Dahlén G. Highly-active antiretroviral therapy and oral opportunistic microorganisms in HIV-positive individuals of Thailand. J Investig Clin Dent. 2016;7(2):158–167. doi: 10.1111/jicd.12142. [DOI] [PubMed] [Google Scholar]
  14. Arirachakaran P, Luangworakhun S, Charalampakis G, Dahlén G. Non-oral, aerobic, Gram-negative bacilli in the oral cavity of Thai HIV-positive patients on Highly-active anti-retrovirus therapy medication. J Investig Clin Dent. 2019;10(2):e12387. doi: 10.1111/jicd.12387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Back-Brito GN, El Ackhar VNR, Querido SMR, dos Santos SSF, Jorge, A…. Koga-Ito, C. Y, Staphylococcus spp., Enterobacteriaceae and Pseudomonadaceae oral isolates from Brazilian HIV-positive patients. Correlation with CD4 cell counts and viral load. Arch Oral Biol. 2011;56:1041–1046. doi: 10.1016/j.archoralbio.2011.02.016. [DOI] [PubMed] [Google Scholar]
  16. Barbosa FC, Mayer MP, Saba-Chujfi E, Cai S. Subgingival occurrence and antimicrobial susceptibility of enteric rods and pseudomonads from Brazilian periodontitis patients. Oral Microbiol Immunol. 2001;16(5):306–310. doi: 10.1034/j.1399-302x.2001.016005306.x. [DOI] [PubMed] [Google Scholar]
  17. Beatty AL, Malloy JL, Wright JR. Pseudomonas aeruginosa degrades pulmonary surfactant and increases conversion in vitro. Am J Respir Cell Mol Biol. 2005;32(2):128–134. doi: 10.1165/rcmb.2004-0276OC. [DOI] [PubMed] [Google Scholar]
  18. Blomqvist S, Leonhardt Å, Arirachakaran P, Carlen A, Dahlén G. Phenotype, genotype, and antibiotic susceptibility of Swedish and Thai oral isolates of Staphylococcus aureus. J Oral Microbiol. 2015;7:26250. doi: 10.3402/jom.v7.26250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Botero JE, Contreras A, Lafaurie G, Jaramillo A, Betancourt M, Arce RM. Occurrence of periodontopathic and superinfecting bacteria in chronic and aggressive periodontitis subjects in a Colombian population. J Periodontol. 2007;78(4):696–704. doi: 10.1902/jop.2007.060129. [DOI] [PubMed] [Google Scholar]
  20. Botero JE, Arce RM, Escudero M, Betancourth M, Jaramillo A, Contreras A. Frequency of detection of periodontopathic and superinfecting bacteria in HIV-positive patients with periodontitis. J Int Acad Periodontol. 2007;9(1):13–18. [PubMed] [Google Scholar]
  21. Carmona IT, Diz Dios P, Scully C. An update on the controversies in bacterial endocarditis of oral origin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93(6):660–670. doi: 10.1067/moe.2002.122338. [DOI] [PubMed] [Google Scholar]
  22. Chinnasamy A, Ramalingam K, Chopra P, Gopinath V, Bishnoi G-P, Chawla G. Chronic nail biting, orthodontic treatment and Enterobacteriaceae in the oral cavity. J Clin Exp Dent. 2019;11:e1157–e1162. doi: 10.4317/jced.56059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cole MF, Bryan S, Evans MK, Pearce CL, Sheridan MJ, Sura PA, Wientzen RL, Bowden GH. Humoral immunity to commensal oral bacteria in human infants : salivary secretory immunoglobulin A antibodies reactive with Streptococcus mitis biovar 1, Streptococcus oralis, Streptococcus mutans, and Enterococcus faecalis during the first two years of life. Infect Immun. 1999;67(4):1878–1886. doi: 10.1128/IAI.67.4.1878-1886.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Colombo AP, Haffajee AD, Dewhirst FE. Clinical and microbiological features of refractory periodontitis subjects. J Clin Periodontol. 1998;25(2):169–180. doi: 10.1111/j.1600-051x.1998.tb02424.x. [DOI] [PubMed] [Google Scholar]
  25. Craig SJC, Blankenberg D, Parodi ACL. Child weight gain trajectories linked to oral microbiota composition. Sci Rep. 2018;8(1):14030. doi: 10.1038/s41598-018-31866-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Cuesta Ai VJ, MiMlAc BNR. Prevalence of Staphylococcus spp and Candida spp in the oral cavity and periodontal pockets of periodontal disease patients. Acta Odontol Latinoam. 2010;23:20–26. [PubMed] [Google Scholar]
  27. Da Silva-Boghossian CM, do Souto RM, Luiz RR, Colombo AP. Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases. Arch Oral Biol. 2011;56(9):899–906. doi: 10.1016/j.archoralbio.2011.02.009. [DOI] [PubMed] [Google Scholar]
  28. Da Silva-Boghossian CM, Neves AB, Resende FAR, Colombo APV. Suppuration-associated bacteria in patients with chronic and aggressive periodontitis. J Periodontol. 2013;84(9):e9–e16. doi: 10.1902/jop.2013.120639. [DOI] [PubMed] [Google Scholar]
  29. Dahlén G. Bacterial infections of the oral mucosa. Periodontol 2000. 2009;49:13–38. doi: 10.1111/j.1600-0757.2008.00295.x. [DOI] [PubMed] [Google Scholar]
  30. Dahlén G, Wikström M. Occurrence of enteric rods, staphylococci and Candida in subgingival samples. Oral Microbiol Immunol. 1995;10(1):42–46. doi: 10.1111/j.1399-302x.1995.tb00116.x. [DOI] [PubMed] [Google Scholar]
  31. Deng DM, Hoogenkamp MA, Exterkate RAM, Jiang LM, van der Sluis, Crielaard W. Influence of Streptococcus mutans on Enterococcus faecalis biofilm formation. J Endod. 2009;35:1249–1252. doi: 10.1016/j.joen.2009.05.038. [DOI] [PubMed] [Google Scholar]
  32. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner ACR, Wade WG. The human oral microbiome. J Bacteriol. 2010;192(19):5002–5017. doi: 10.1128/JB.00542-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Edwardsson S, Bing M, Axtelius B, Lindberg B, Söderfeldt B, Attström R. The microbiota of periodontal pockets with different depths in therapy-resistant periodontitis. J Clin Periodontol. 1999;26(3):143–152. doi: 10.1034/j.1600-051X.1999.260303.x. [DOI] [PubMed] [Google Scholar]
  34. Ewan VC, Sails AD, Walls AWG, Rushton S, Newton JL. Dental and microbiological risk factors for hospital-acquired pneumonia in non-ventilated older patients. PLoS One. 2015;10:e0123622. doi: 10.1371/journal.pone.0123622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Fritschi BZ, Albert-Kiszely A, Persson GR. Staphylococcus aureus and other bacteria in untreated periodontitis. J Dent Res. 2008;87(6):589–593. doi: 10.1177/154405910808700605. [DOI] [PubMed] [Google Scholar]
  36. Gao L, Xu T, Huang G, Jiang S, GuChen YF. Oral microbiomes : more and more importance in oral cavity and whole body. Protein Cell. 2018;9(5):488–500. doi: 10.1007/s13238-018-0548-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ghapanchi J, Emami A, Rezazadeh F, Shakibasefat H, Pirbonyeh N. Isolation of Enterococcus faecalis in the saliva samples of patient candidates for liver transplantation. J Dent Res. 2019;16(5):333–337. doi: 10.4103/1735-3327.266091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Gibson J, Wray D, Bagg J. Oral staphylococcal mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89(2):171–176. doi: 10.1067/moe.2000.101810. [DOI] [PubMed] [Google Scholar]
  39. Gonçalves LS, Soares FSM, Souza CO, Souto R, Colombo AP. Clinical and microbiological profiles of human immunodeficiency virus (HIV)-seropositive Brazilians undergoing highly active antiretroviral therapy and HIV-seronegative Brazilians with chronic periodontitis. J Periodontol. 2007;78(1):87–96. doi: 10.1902/jop.2007.060040. [DOI] [PubMed] [Google Scholar]
  40. Gonçalves MO, Coutinho-Filho WP, Pimenta FP, Pereira GA, Mattos-Guaraldi AL, Hirata R. Periodontal disease as reservoir for multi-resistant and hydrolytic enterobacterial species. Lett Appl Microbiol. 2007;44(5):488–494. doi: 10.1111/j.1472-765X.2007.02111.x. [DOI] [PubMed] [Google Scholar]
  41. Gosney M, Punekar S, Playfer JR, Bilsborrow PK, Martin MV. The incidence of oral Gram-negative bacteria in patients with Parkinson’s disease. Eur J Intern Med. 2003;14(8):484–487. doi: 10.1016/j.ejim.2003.09.009. [DOI] [PubMed] [Google Scholar]
  42. Handal T, Caugant DA, Olsen I. Antibiotic resistance in bacteria isolated from subgingival plaque in a Norwegian population with refractory marginal periodontitis. Antimicrob Agents Chemother. 2003;47(4):1443–1446. doi: 10.1128/aac.47.4.1443-1446.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Jackson MS, Bagg J, Gupta MN, Sturrock RD. Oral carriage of staphylococci in patients with rheumatoid arthritis. Rheumatology. 1999;38(6):572–575. doi: 10.1093/rheumatology/38.6.572. [DOI] [PubMed] [Google Scholar]
  44. Jacobson JJ, Patel B, Asher G, Woolliscroft JO, Schaberg D. Oral Staphylococcus in older subjects with rheumatoid arthritis. J Am Geriatr Soc. 1997;45(5):590–593. doi: 10.1111/j.1532-5415.1997.tb03092.x. [DOI] [PubMed] [Google Scholar]
  45. Johnson EM, Flannagan SE, Sedgley CM. Coaggregation interactions between oral and endodontic Enterococcus faecalis and bacterial species isolated from persistent apical periodontitis. J Endod. 2006;32(10):946–950. doi: 10.1016/j.joen.2006.03.023. [DOI] [PubMed] [Google Scholar]
  46. Kamaguchi A, Nakayama K, Ichiyama S, Nakamura R, Watanabe T, Ohyama T. Effect of Porphyromonas gingivalis vesicles on coaggregation of Staphylococcus aureus to oral microorganisms. Curr Microbiol. 2003;47(12):485–91. doi: 10.1007/s00284-003-4069-6. [DOI] [PubMed] [Google Scholar]
  47. Kang MS, Na HS, Oh JS. Coaggregation ability of Weissella cibaria isolates with Fusobacterium nucleatum and their adhesiveness to epithelial cells. FEMS Microbiol Lett. 2005;253(2):323–329. doi: 10.1016/j.femsle.2005.10.002. [DOI] [PubMed] [Google Scholar]
  48. Kart D, Yabanoglu Ciftci S, Nemutlu E. Altered metabolomic profile of dual-species biofilm: Interactions between Proteus mirabilis and Candida albicans. Microbiol Res. 2020;230:126346. doi: 10.1016/j.micres.2019.126346. [DOI] [PubMed] [Google Scholar]
  49. Kayaoglu G, Ørstavik D. Virulence factors of Enterococcus faecalis: relationship to endodontic disease. Crit Rev Oral Biol Med. 2004;15(5):308–320. doi: 10.1177/154411130401500506. [DOI] [PubMed] [Google Scholar]
  50. Kazemian H, Bourbour S, Beheshti M, Bahador A. Oral colonization by nosocomial pathogens during hospitalization in intensive care unit and prevention strategies. Recent Pat Antiinfect Drug Discov. 2017;12(1):8–20. doi: 10.2174/1574891X12666170215152854. [DOI] [PubMed] [Google Scholar]
  51. Kearney A, Kinnevey P, Shore A. The oral cavity revealed as a significant reservoir of Staphylococcus aureus in an acute hospital by extensive patient, healthcare worker and environmental sampling. J Hosp Infect. 2020;S0195–6701(20):30103–30111. doi: 10.1016/j.jhin.2020.03.004. [DOI] [PubMed] [Google Scholar]
  52. Kolenbrander PE. Oral microbial communities: biofilms, interactions, and genetic systems. Annu Rev Microbiol. 2000;54:413–437. doi: 10.1146/annurev.micro.54.1.413. [DOI] [PubMed] [Google Scholar]
  53. Kolenbrander PE, Palmer RJ, Periasamy S, Jakubovics NS. Oral multispecies biofilm development and the key role of cell-cell distance. Nat Rev Microbiol. 2010;8(7):471–480. doi: 10.1038/nrmicro2381. [DOI] [PubMed] [Google Scholar]
  54. Komiyama K, Gibbons RJ. Interbacterial adherence between Actinomyces viscosus and strains of Streptococcus pyogenes, Streptococcus agalactiae, and Pseudomonas aeruginosa. Infect Immun. 1984;44(1):86–90. doi: 10.1128/iai.44.1.86-90.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Komiyama K, Tynan JJ, Habbick BF, Duncan DE, Liepert DJ. Pseudomonas aeruginosa in the oral cavity and sputum of patients with cystic fibrosis. Oral Surg Oral Med Oral Pathol. 1985;59:590–594. doi: 10.1016/0030-4220(85)90187-2. [DOI] [PubMed] [Google Scholar]
  56. Komiyama K, Habbick BF, Gibbons RJ. Interbacterial adhesion between Pseudomonas aeruginosa and indigenous oral bacteria isolated from patients with cystic fibrosis. Can J Microbiol. 1987;33(1):27–32. doi: 10.1139/m87-005. [DOI] [PubMed] [Google Scholar]
  57. Komiyama EY, Lepesqueur LSS, Yassuda CG, Samaranayake LP, Parahitiyawa NB, Balducci I, Koga-Ito CY. Enterococcus species in the oral cavity : prevalence, virulence factors and antimicrobial susceptibility. PLoS One. 2016;11(9):e0163001. doi: 10.1371/journal.pone.0163001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Kouidhi B, Zmantar T, Mahdouani K, Hentati H, Bakhrouf A. Antibiotic resistance and adhesion properties of oral Enterococci associated to dental caries. BMC Microbiol. 2011;11:155. doi: 10.1186/1471-2180-11-155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Kreth J, Merritt J, Qi F. Bacterial and host interactions of oral streptococci. DNA Cell Biol. 2009;28(8):397–403. doi: 10.1089/dna.2009.0868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Leão-Vasconcelos LS, Lima AB, Costa DM. Enterobacteriaceae isolates from the oral cavity of workers in a Brazilian oncology hospital. Rev Inst Med Trop Sao Paulo. 2015;57(2):121–127. doi: 10.1590/S0036-46652015000200004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Lee YT, Fung CP, Wang FD, Chen CP, Chen TL, Cho WL. Outbreak of imipenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex harboring different carbapenemase gene-associated genetic structures in an intensive care unit. J Microbiol Immunol Infect. 2012;45(1):43–51. doi: 10.1016/j.jmii.2011.09.020. [DOI] [PubMed] [Google Scholar]
  62. Li X, Hoogenkamp MA, Ling J, Crielaard W, Deng DM. Diversity of Streptococcus mutans strains in bacterial interspecies interactions. J Basic Microbiol. 2014;54(2):97–103. doi: 10.1002/jobm.201200457. [DOI] [PubMed] [Google Scholar]
  63. Lima BP, Shi W, Lux R. Identification and characterization of a novel Fusobacterium nucleatum adhesin involved in physical interaction and biofilm formation with Streptococcus gordonii. Microbiologyopen. 2017;6(3):e00444. doi: 10.1002/mbo3.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Lima BP, Hu LI, Vreeman GW, Weibel DB, Lux R. The oral bacterium Fusobacterium nucleatum binds Staphylococcus aureus and alters expression of the staphylococcal accessory regulator sarA. Microb Ecol. 2019;78(2):336–347. doi: 10.1007/s00248-018-1291-0. [DOI] [PubMed] [Google Scholar]
  65. Lins RX, Hirata R, Wilson M, Lewis MAO, Fidel RAS, Williams D. Comparison of genotypes, antimicrobial resistance and virulence profiles of oral and non oral Enterococcus faecalis from Brazil, Japan and the United Kingdom. J Dent. 2019;84:49–54. doi: 10.1016/j.jdent.2019.03.002. [DOI] [PubMed] [Google Scholar]
  66. Listgarten MA, Lai CH, Lai CH. Comparative microbiological characteristics of failing implants and periodontally diseased teeth. J Periodontol. 1999;70(4):431–437. doi: 10.1902/jop.1999.70.4.431. [DOI] [PubMed] [Google Scholar]
  67. Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis. 2002;34(5):634–640. doi: 10.1086/338782. [DOI] [PubMed] [Google Scholar]
  68. Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339(8):520–532. doi: 10.1056/NEJM199808203390806. [DOI] [PubMed] [Google Scholar]
  69. Mahasneh SA, Mahasneh AM. Probiotics: a promising role in dental health. J Dent. 2017;5(4):26. doi: 10.3390/dj5040026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Martínez-Lamas L, Constenla-Caramés L, Otero-Fernández S, Álvarez-Fernández M. New clone of ST-187 Acinetobacter baumannii responsible for an outbreak in an intensive care unit. Enferm Infecc Microbiol Clin. 2014;32(4):242–245. doi: 10.1016/j.eimc.2013.10.014. [DOI] [PubMed] [Google Scholar]
  71. Martínez-Pabón MC, Isaza-Guzmán DM, Mira-López NR, García-Vélez C, Tobón-Arroyave SI. Screening for subgingival occurrence of gram-negative enteric rods in periodontally diseased and healthy subjects. Arch Oral Biol. 2010;55(10):728–736. doi: 10.1016/j.archoralbio.2010.07.008. [DOI] [PubMed] [Google Scholar]
  72. Merghni A, Ben Nejma M, Hentati H, Mahjoub A, Mastouri M. Adhesive properties and extracellular enzymatic activity of Staphylococcus aureus strains isolated from oral cavity. Microb Pathog. 2014;73:7–12. doi: 10.1016/j.micpath.2014.05.002. [DOI] [PubMed] [Google Scholar]
  73. Merghni A, Ben Nejma M, Helali I, Hentati H, Bongiovanni A, Mastouri M. Assessment of adhesion, invasion and cytotoxicity potential of oral Staphylococcus aureus strains. Microb Pathog. 2015;86:1–9. doi: 10.1016/j.micpath.2015.05.010. [DOI] [PubMed] [Google Scholar]
  74. Nakou M, Kamma J, Gargalianos P, Laskaris G, Mitsis F. Periodontal microflora of HIV infected patients with periodontitis. Anaerobe. 1997;3(2–3):97–102. doi: 10.1006/anae.1997.0081. [DOI] [PubMed] [Google Scholar]
  75. Okuda K, Kimizuka R, Katakura A, Nakagawa T, Ishihara K. Ecological and immunopathological implications of oral bacteria in Helicobacter pylori infected disease. J Periodontol. 2003;74(1):123–128. doi: 10.1902/jop.2003.74.1.123. [DOI] [PubMed] [Google Scholar]
  76. Okui A, Soga Y, Kokeguchi S, Nose M, Yamanaka R, Kusano N, Morita M. Detection of identical isolates of Enterococcus faecalis from the blood and oral mucosa in a patient with infective endocarditis. Intern Med J. 2015;54(14):1809–1814. doi: 10.2169/internalmedicine.54.3223. [DOI] [PubMed] [Google Scholar]
  77. Panghal M, Kaushal V, Yadav JP. In vitro antimicrobial activity of ten medicinal plants against clinical isolates of oral cancer cases. Ann Clin Microbiol Antimicrob. 2011;10:21. doi: 10.1186/1476-0711-10-21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Park J, Shokeen B, Haake SK, Lux R. Characterization of Fusobacterium nucleatum ATCC 23726 adhesins involved in strain-specific attachment to Porphyromonas gingivalis. Int J Oral Sci. 2016;8(3):138–144. doi: 10.1038/ijos.2016.27. [DOI] [Google Scholar]
  79. Pereira CA, Toledo BC, Santos CT, Pereira Costa ACB, Back-Brito GN, Jorge AOC. Opportunistic microorganisms in individuals with lesions of denture stomatitis. Diagn Microbiol Infect Dis. 2013;76(4):419–424. doi: 10.1016/j.diagmicrobio.2013.05.001. [DOI] [PubMed] [Google Scholar]
  80. Persson GR, Renvert S. Cluster of bacteria associated with peri-implantitis. Clin Implant Dent Relat Res. 2014;16(6):783–793. doi: 10.1111/cid.12052. [DOI] [PubMed] [Google Scholar]
  81. Persson GR, Hitti J, Paul K, Hirschi R, Weibel M, Rothen M, Persson RE. Tannerella forsythia and Pseudomonas aeruginosa in subgingival bacterial samples from parous women. J Periodontol. 2008;79(3):508–516. doi: 10.1902/jop.2008.070350. [DOI] [PubMed] [Google Scholar]
  82. Pihl M, Chávez de Paz LE, Schmidtchen A, Svensäter G, Davies JR. Effects of clinical isolates of Pseudomonas aeruginosa on Staphylococcus epidermidis biofilm formation. FEMS Immunol Med Microbiol. 2010;59(3):504–512. doi: 10.1111/j.1574-695X.2010.00707.x. [DOI] [PubMed] [Google Scholar]
  83. Priyadharsini VJ, Smiline Girija AS, Paramasivam A. In silico analysis of virulence genes in an emerging dental pathogen A. baumannii and related species. Arch Oral Biol. 2018;94:93–98. doi: 10.1016/j.archoralbio.2018.07.001. [DOI] [PubMed] [Google Scholar]
  84. Rams TE, Andriolo M, Feik D, Abel SN, McGivern TM, Slots J. Microbiological study of HIV-related periodontitis. J Periodontol. 1991;62(1):74–81. doi: 10.1902/jop.1991.62.1.74. [DOI] [PubMed] [Google Scholar]
  85. Ranganathan AT, Sarathy S, Chandran CR, Iyan K. Subgingival prevalence rate of enteric rods in subjects with periodontal health and disease. J Indian Soc Periodontol. 2017;21(3):224–228. doi: 10.4103/jisp.jisp_204_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Richards AM, Abu Kwaik Y, Lamont RJ. Code blue: Acinetobacter baumannii, a nosocomial pathogen with a role in the oral cavity. Mol Oral Microbiol. 2015;30(1):2–15. doi: 10.1111/omi.12072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Rivas Caldas R, Le Gall F, Revert K, Rault G, Virmaux Boisramé MS. Pseudomonas aeruginosa and periodontal pathogens in the oral cavity and lungs of cystic fibrosis patients : a case-control study. J Clin Microbiol. 2015;53(6):1898–1907. doi: 10.1128/JCM.00368-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Scannapieco FA, Yu J, Raghavendran K, Vacanti A, Owens SI, Mylotte JM. A randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients. Crit Care. 2009;13(4):R117. doi: 10.1186/cc7967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Scoffield JA, Wu H. Oral streptococci and nitrite-mediated interference of Pseudomonas aeruginosa. Infect Immun. 2015;83(1):101–107. doi: 10.1128/IAI.02396-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Sedgley CM, Lennan SL, Clewell DB. Prevalence, phenotype and genotype of oral enterococci. Oral Microbiol Immunol. 2004;19(2):95–101. doi: 10.1111/j.0902-0055.2004.00122.x. [DOI] [PubMed] [Google Scholar]
  91. Sedgley CM, Lennan SL, Appelbe OK. Survival of Enterococcus faecalis in root canals ex vivo. Int Endod J. 2005;38(10):735–742. doi: 10.1111/j.1365-2591.2005.01009.x. [DOI] [PubMed] [Google Scholar]
  92. Sedgley C, Buck G, Appelbe O. Prevalence of Enterococcus faecalis at multiple oral sites in endodontic patients using culture and PCR. J Endod. 2006;32(2):104–109. doi: 10.1016/j.joen.2005.10.022. [DOI] [PubMed] [Google Scholar]
  93. Simões-Silva L, Ferreira S, Santos-Araujo C. Oral Colonization of Staphylococcus species in a peritoneal dialysis population: a possible reservoir for PD-related infections? Can J Infect Dis Med Microbiol. 2018;2018:5789094. doi: 10.1155/2018/5789094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Slots J, Rams TE, Schonfeld SE. In vitro activity of chlorhexidine against enteric rods, pseudomonas and acinetobacter from human periodontitis. Oral Microbiol Immunol. 1991;6(1):62–64. doi: 10.1111/j.1399-302x.1991.tb00452.x. [DOI] [PubMed] [Google Scholar]
  95. Smith RS, Iglewski BH. P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol. 2003;6(1):56–60. doi: 10.1016/s1369-5274(03)00008-0. [DOI] [PubMed] [Google Scholar]
  96. Smith AJ, Jackson MS, Bagg J. The ecology of Staphylococcus species in the oral cavity. J Med Microbiol. 2001;50(11):940–946. doi: 10.1099/0022-1317-50-11-940. [DOI] [PubMed] [Google Scholar]
  97. Smith AJ, Brewer A, Kirkpatrick P, Jackson MS, Young J, Watson S, Thakker B. Staphylococcal species in the oral cavity from patients in a regional burns unit. J Hosp Infect. 2003;55(3):184–189. doi: 10.1016/j.jhin.2003.08.004. [DOI] [PubMed] [Google Scholar]
  98. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25(2):134–144. doi: 10.1111/j.1600-051x.1998.tb02419.x. [DOI] [PubMed] [Google Scholar]
  99. Soni P, Parihar RS, Soni LK. Opportunistic microorganisms in oral cavity according to treatment status in head and neck cancer patients. J Clin Diagn Res. 2017;11(9):DC14–DC17. doi: 10.7860/JCDR/2017/27284.10635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Souto R, Colombo APV. Prevalence of Enterococcus faecalis in subgingival biofilm and saliva of subjects with chronic periodontal infection. Arch Oral Biol. 2008;53(2):155–160. doi: 10.1016/j.archoralbio.2007.08.004. [DOI] [PubMed] [Google Scholar]
  101. Souto R, Colombo APV. Detection of Helicobacter pylori by polymerase chain reaction in the subgingival biofilm and saliva of non-dyspeptic periodontal patients. J Periodontol. 2008;79(1):97–103. doi: 10.1902/jop.2008.070241. [DOI] [PubMed] [Google Scholar]
  102. Souto R, de Andrade AFB, Uzeda M, Colombo APV. Prevalence of non-oral pathogenic bacteria in subgingival biofilm of subjects with chronic periodontitis. Braz J Microbiol. 2006;37(3):208–215. doi: 10.1590/S1517-83822006000300002. [DOI] [Google Scholar]
  103. Souto R, Silva-Boghossian CM, Colombo APV. Prevalence of Pseudomonas aeruginosa and Acinetobacter spp In subgingival biofilm and saliva of subjects with chronic periodontal infection. Braz. J. Microbiol. 2014;45(2):495–501. doi: 10.1590/S1517-83822014000200017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Souza LCD, Lopes FF, Bastos EG, Alves MC. Oral infection by Pseudomonas aeruginosa in patient with chronic kidney disease - a case report. J Bras Nefrol. 2018;40(1):82–85. doi: 10.1590/1678-4685-JBN-3812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Tada A, Hanada N. Opportunistic respiratory pathogens in the oral cavity of the elderly. FEMS Immunol Med Microbiol. 2010;60(1):1–17. doi: 10.1111/j.1574-695X.2010.00709.x. [DOI] [PubMed] [Google Scholar]
  106. Tawara Y, Honma K, Naito Y. Methicillin-resistant Staphylococcus aureus and Candida albicans on denture surfaces. Bull Tokyo Dent Coll. 1996;37(3):119–128. [PubMed] [Google Scholar]
  107. Thurnheer T, Belibasakis GN. Integration of non-oral bacteria into in vitro oral biofilms. Virulence. 2015;6(3):258–264. doi: 10.4161/21505594.2014.967608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Uehara Y, Kikuchi K, Nakamura T. Inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns by viridans group streptococci. Clin Infect Dis. 2001;32(10):1399–1407. doi: 10.1086/320147. [DOI] [PubMed] [Google Scholar]
  109. Van Winkelhoff AJ, Rurenga P, Wekema-Mulder GJ, Singadji ZM, Rams TE. Non-oral gram-negative facultative rods in chronic periodontitis microbiota. Microb Pathog. 2016;94:117–122. doi: 10.1016/j.micpath.2016.01.020. [DOI] [PubMed] [Google Scholar]
  110. Vidana R, Sullivan A, Billström H, Ahlquist M, Lund B. Enterococcus faecalis infection in root canals—host-derived or exogenous source? Lett Appl Microbiol. 2011;52(2):109–115. doi: 10.1111/j.1472-765X.2010.02972.x. [DOI] [PubMed] [Google Scholar]
  111. Vieira Colombo AP, Magalhães CB, Hartenbach FARR, Martins do SoutoMaciel da Silva-Boghossian RC. Periodontal-disease-associated biofilm : a reservoir for pathogens of medical importance. Microb Pathog. 2016;94:27–34. doi: 10.1016/j.micpath.2015.09.009. [DOI] [PubMed] [Google Scholar]
  112. Wade WG. The oral microbiome in health and disease. Pharmacol Res. 2013;69(1):137–143. doi: 10.1016/j.phrs.2012.11.006. [DOI] [PubMed] [Google Scholar]
  113. Wang L, Dong M, Zheng J, Song Q, Yin W, Li J, Niu W. Relationship of biofilm formation and gelE gene expression in Enterococcus faecalis recovered from root canals in patients requiring endodontic retreatment. J Endod. 2011;37(5):631–636. doi: 10.1016/j.joen.2011.02.006. [DOI] [PubMed] [Google Scholar]
  114. Watanabe K, Senba M, Ichinose A, Yamamoto T, Ariyoshi K, Matsumoto K. Bactericidal activity in filtrated supernatant of Streptococcus sanguinis against multidrug-resistant Pseudomonas aeruginosa. Tohoku J Exp Med. 2009;219(2):79–84. doi: 10.1620/tjem.219.79. [DOI] [PubMed] [Google Scholar]
  115. World Health Organization (2017) Global priority list of antibiotic-resistant bacteria to guide research, discovery and development of new antibiotics. https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/
  116. Yamashita K, Ohara M, Kojima T, Nishimura R, Ogawa T, Hino T, et al. Prevalence of drug-resistant opportunistic microorganisms in oral cavity after treatment for oral cancer. J Oral Sci. 2013;55(2):145–155. doi: 10.2334/josnusd.55.145. [DOI] [PubMed] [Google Scholar]
  117. Zarco MF, Vess TJ, Ginsburg GS. The oral microbiome in health and disease and the potential impact on personalized dental medicine. Oral Dis. 2012;18(2):109–120. doi: 10.1111/j.1601-0825.2011.01851.x. [DOI] [PubMed] [Google Scholar]
  118. Zehnder M, Guggenheim B. The mysterious appearance of enterococci in filled root canals. Int Endod J. 2009;42(4):277–287. doi: 10.1111/j.1365-2591.2008.01537.x. [DOI] [PubMed] [Google Scholar]
  119. Zhu HW, McMillan AS, McGrath C, Li LSW, Samaranayake LP. Oral carriage of yeasts and coliforms in stroke sufferers: a prospective longitudinal study. Oral Dis. 2008;14(1):60–66. doi: 10.1111/j.1601-0825.2006.01347.x. [DOI] [PubMed] [Google Scholar]
  120. Zhu X, Wang Q, Zhang C, Cheung GSP, Shen Y. Prevalence, phenotype, and genotype of Enterococcus faecalis isolated from saliva and root canals in patients with persistent apical periodontitis. J Endod. 2010;36(12):1950–1955. doi: 10.1016/j.joen.2010.08.053. [DOI] [PubMed] [Google Scholar]
  121. Zuanazzi D, Souto R, Mattos MBA, Zuanazzi MR, Tura BR, Sansone C, Colombo APV. Prevalence of potential bacterial respiratory pathogens in the oral cavity of hospitalised individuals. Arch Oral Biol. 2010;55(1):21–28. doi: 10.1016/j.archoralbio.2009.10.005. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials


Articles from Archives of Microbiology are provided here courtesy of Nature Publishing Group

RESOURCES