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. 2022 Jun 9;68(3):200–207. doi: 10.14789/jmj.JMJ21-0057-R

Emergence of Carbapenem-resistant Clinical Isolates of Providencia Species

SHU IWATA 1, TATSUYA TADA 1, SATOSHI OSHIRO 1, TOMOMI HISHINUMA 1, MARI TOHYA 1, TERUO KIRIKAE 1,✉
PMCID: PMC11250026  PMID: 39021729

Abstract

Providencia is a genus of Gram-negative and non-spore forming bacteria belonging to the family Morganellaceae, which causes opportunistic infections in humans. Of the 10 Providencia species identified to date, three, P. alcalifaciens, P. rettgeri and P. stuartii, are clinically important. P. alcalifaciens causes diarrhea, including outbreaks arising from food-borne infections, and P. stuartii and P. rettgeri have been found to cause hospital acquired urinary tract infections. Four isolates of P. rettgeri and one isolate of P. stuartii were obtained from urine samples of five patients in Japan in 2018. All five isolates were highly resistant to carbapenems. Three isolates harbored blaIMP-70, encoding a variant of IMP-1 metallo-β-lactamase, with two amino acid substitutions (Val67Phe and Phe87Val), one isolate harbored two copies of blaIMP-1 and one isolate harbored blaIMP-11. Expression of blaIMP-70 conferred carbapenem resistance in Escherichia coli. Recombinant IMP-10, an IMP-1 variant with Val67Phe but without Phe87Val, had significant higher hydrolytic activities against meropenem than recombinant IMP-1, indicating that the Val67Phe amino acid substitution alters activities against meropenem in IMP-70. These results suggest that Providencia species. become more highly resistant to carbapenems by acquisition of two copies of blaIMP-1 or by mutations in blaIMP that result in amino acid substitutions, such as blaIMP-70.

Key words: Providencia rettgeri, Providencia stuartti, metallo-β-lactamase

Taxonomy of the Providencia genus

Providencia, a genus of Gram-negative and non- spore forming bacteria, was originally assigned to the family Enterobacteriaceae, but has recently been assigned to the family Morganellaceae1). Species of Providencia genus have been isolated from many vertebrate and invertebrate animals, including humans and insects2-4), and causes opportunistic infections in humans5). To date, 10 species belonging to the genus Providencia have been identified: P. alcalifaciens, P. burhodogranariea, P. heimbachae, P. huaxiensis, P. rettgeri, P. rustigianii, P. sneebia, P. stuartii, P. thailandensis and P. vermicola. Of these 10 species of Providencia, five, P. alcalifaciens, P. friedericiana (synonym of P. rustigianii), P. rettgeri, P. stuartii and P. vermicola, were isolated from humans, with three of these, P. alcalifaciens, P. rettgeri and P. stuartii, likely to be clinically important5, 6). A phylogenetic tree based on whole genome sequences of the 10 Providencia species revealed that these species consist of three clusters, with the five species isolated from humans, being spread among these three clusters (Figure 1). These findings indicate that the genus Providencia does not have a subgenus associated with human infections. The five species were found to have specific genes associated with human infections, such as genes encoding adherence and invasion factors.

Figure 1.

Figure 1

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Maximum-likelihood (ML) tree based on single nucleotide polymorphisms (SNPs) in the core genome among contigs of strains, showing the relationships among type strains of the genus Providencia. Bootstrap values, expressed as percentages of 1,000 replications, are shown at the branching points when >50 %.

Providencia species as human pathogens

A study of the enteropathogenicity of P. alcalifaciens isolated from a child and two adults with diarrhea demonstrated that this species causes diarrhea in humans by invading the intestinal mucosal epithelium7). P. alcalifaciens was subsequently isolated from 2.1% of the stool specimens of diarrheal children younger than 5 years of age, indicating that this organism is significantly associated with diarrhea8). A large outbreak of food-borne infection caused by P. alcalifaciens occurred among children and teachers at two kindergartens and one high school in November 1996 in Fukui, Japan9). Specifically, of the 610 children and teachers who ate lunch cooked at a single catering facility, 270 showed symptoms of gastroenteritis9). Recent outbreaks of P. alcalifaciens have indicated that infection with this organism is a public health concern in both developing and developed countries10). Although epidemiological studies suggest that P. alcalifaciens causes diarrhea by invading the intestinal mucosa10), the pathogenesis of P. alcalifaciens has not been established at the molecular level.

P. stuartii and P. rettgeri have been found to cause hospital acquired urinary tract infections11) and have been shown to be the most common causes of urinary tract infections in hospitalized patients. In addition, P. stuartii and P. rettgeri have been found to cause pneumonia, meningitis, endocarditis, wound infections and bloodstream infections11), and P. stuartii was found to cause invasive endocarditis12) and neonatal sepsis13). P. alcalifaciens, P. rettgeri and P. stuartii were isolated from 17.6% of stool samples of patients with diarrhea at the Kansai airport quarantine station in 2002, with vomiting being especially frequent in patients infected with P. rettgeri, indicating that these three Providencia species cause travelers' diarrhea5).

Emergence of carbapenem-resistant Providencia species

The emergence and spread of carbapenem-resistant Gram-negative pathogens have become serious public health problems worldwide14). Most of these carbapenem-resistant isolates produce metallo-β-lactamases (MBLs), including IMP-, NDM- and VIM-type MBLs14), which confer high resistance against all β-lactams (penicillins, cephalosporines and carbapenems) except for monobactams15). Clinical isolates of carbapenem-resistant P. rettgeri producing IMP-1 MBL were first identified by laboratory-based surveillance in the Kinki region of Japan in 200016). Clinical isolates of P. stuartii producing VIM-19 MBL were first identified in 2008 in Algeria17). To date, there have been 16 reports of carbapenem-resistant P. rettgeri, eight of carbapenem-resistant P. stuartii and one of carbapenem-resistant P. vermicola (Table 1). Most of these were clinical isolates, but one was obtained from a hospital environment and one from pet turtles (Table 1).

Table 1.

Reports of P. rettgeri, P. stuartii and P. vermicola producing MBLa

Species Metallo-β-lactamase Location of
MBL-encoding gene		 Inc type Isolation source Isolated year Isolated country Reference
P. rettgeri IMP-1 - - - 2000 Japan 16)
IMP-1 plasmid - sputum, blood 2002 Japan 25)
IMP-1 chromosome urine 2018 Japan 18)
IMP-11 plasmid (84,930-bp) IncT urine 2018 Japan 18)
IMP-27 plasmid (10,7365-bp) IncQ wound 2016 USA 26)
IMP-27 - - pet turtles 2018 Korea 27)
IMP-70 plasmid (204,791-bp) IncA/C2 urine 2018 Japan 18)
NDM-1 - - blood, rectum, pus 2008 Israel 28)
2011
NDM-1 plasmid - sputum, pus 2012 Nepal 29)
NDM-1 plasmid (178kb) - urine 2012 Mexico 30)
NDM-1 plasmid (190kb) IncA/C urine 2014 China 31)
NDM-1 - - - 2017 Bulgaria 32)
NDM - - wound 2013 Brazil 33)
NDM-1, VIM-2 plasmid - urine 2015 Colombia 34)
NDM-18 plasmid - effluent from
a pediatric ward		 2017 South Africa 35)
P. stuartii IMP-70 plasmid (152,754-bp) IncA/C urine 2018 Japan 18)
NDM-1 plasmid (178277kb) IncA/C blood 2012 Afghanistan 36)
NDM-1 plasmid (18,480-bp) IncA/C2 urine 2020 Peru 37)
VIM-1 - - - 2011 Greece 38)
VIM-1 plasmid (180kb) IncA/C rectum 2012 Greece 39)
VIM-1 plasmid - - 2013 Greece 40)
VIM-2 - - urine 2004 Korea 41)
VIM-19 plasmid (180kb) - - 2008 Algeria 17)
P. vermicola NDM-1 plasmid (151,684-bp) - blood 2017 Congo 42)
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a Iwata S, Tada T, Hishinuma T, et al: Antimicrob Agents Chemother, 2020; 64.18)

A dash (–) indicates there was no information about the location of MBL-encoding genes, Inc type and isolation source.

All of these isolates produced MBLs, with the majority of carbapenem-resistant P. rettgeri isolates producing IMP-type or NDM-type MBLs (Table 1). IMP-type MBLs were detected in isolates from Japan, Korea, and the United States, whereas NDM- type MBLs were detected in isolates worldwide. We obtained four clinical isolates of carbapenem- resistant P. rettgeri, which produced IMP-1, IMP-11 or IMP-70. One IMP-1 producing isolate was from Saitama, Japan, one IMP-11 producing isolate was from Kochi, Japan, and two IMP-70 producing isolates were from Osaka, Japan18).

Most of the carbapenem-resistant P. stuartii isolates, obtained in Algeria, Greece and Korea, produced VIM-type MBLs. Carbapenem-resistant P. stuartii isolates producing NDM-type MBL- producing P. stuartii were obtained in Afghanistan and Peru, and we described an IMP-type MBL- producing P. stuartii from Japan18). Carbapenem- resistant P. vermicola isolates producing NDM-1 were isolated in the Congo.

Carbapenem-resistant clinical isolates of Providencia species in Japan

We obtained four clinical isolates of P. rettgeri and one clinical isolate of P. stuartii from the urine samples of five patients in Japan in 201818). All five were multidrug-resistant, being resistant to aminoglycosides, carbapenems and fluoroquinolones18). These isolates harbored genes encoding aminoglycoside modifying enzymes, including aac(6’)-Ib4 and aac(6’)-Iae, and MBL genes encoding carbapenemases; including IMP-1, IMP-11 and IMP-70 (Table 2). They also had three mutations with amino acid substitutions in GyrA and ParC, which were associated with quinolone resistance (Table 2). One isolate harbored aminoglycoside- and carbapenem-resistant genes on the chromosome, whereas the other four harbored these genes on plasmids.

Table 2.

Genetic characterization of carbapenem-resistant Providencia species isolatesa

isolates genome size (bp) antibiotic resistance genes quinolone resistance genes
aminoglycosides carbapenemase GyrA ParC
P. rettgeri BML2496 chromosome 4.65M aac(6’)-Ib4 bla IMP - 1 Ser83Ile
Asp87Ala		 Ser87Ile
P. rettgeri BML2526 chromosome 4.34M Ser83Ile
Asp87Glu		 Ser87Ile
plasmid 205K aac(6’)-Iae bla IMP - 70
P. rettgeri BML2531 chromosome 4.70M Ser83Ile
Asp87Glu		 Ser87Ile
plasmid 85K aac(6’)-Il bla IMP - 11
P. rettgeri BML2576 chromosome 4.35M Ser83Ile
Asp87Glu		 Ser87Ile
plasmid 205K aac(6’)-Iae bla IMP - 70
P. stuartii BML2537 chromosome 4.42M aac(2’)-Ia Ser83Ile
Asp87Glu		 Ser87Arg
plasmid 153K aac(6’)-Iae bla IMP - 70
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a Iwata S, Tada T, Hishinuma T, et al: Antimicrob Agents Chemother, 2020; 64.18)

Carbepenemase activities of IMP-1 MBL variants

All five P. rettgeri and P. stuartii clinical isolates were resistant to imipenem and meropenem, and three, two P. rettgeri isolates and one P. stuartii isolate, were highly resistant to both carbapenems, with minimum inhibitory concentrations (MICs) of 512 μg/ml (Table 3). These three highly carbapenem-resistant isolates harbored blaIMP-70, whereas, of the other two, one harbored blaIMP-1 and the other harbored blaIMP-11. IMP-70 is a variant of IMP-1 with two amino acid substitutions, Val67Phe and Phe87Val; IMP-10 is a variant of IMP-1 with one amino acid substitution, Val67Phe; and IMP- 1(F87V) is a variant of IMP-1 with one amino acid substitution, Phe87Val. E. coli expressing blaIMP-1, blaIMP-10, blaIMP-1(Phe87Val), and blaIMP-70 showed significantly higher MICs for all carbapenems tested than a vector control (Table 4). The MICs for all carbapenems of the vector control ranged from ≤0.06 to 0.125. E. coli expressing blaIMP-70 showed higher MICs for doripenem and meropenem, but the same MICs for imipenem and panipenem, than E. coli expressing blaIMP-1. E. coli expressing blaIMP-10 showed a significantly higher MIC for doripenem and an increased MIC for meropenem. Assessment of the carbepenemase activities of recombinant IMP-1, IMP-10, IMP-1(Phe87Val) and IMP-70 showed that IMP-10 had greater hydrolytic activities than IMP-1 against meropenem, with the kcat/Km values of IMP-70 and IMP-10 being 2.3- and 3.4-fold higher, respectively, than those of IMP-1 (Table 5). In contrast IMP-70 and IMP-1 showed similar carbapenemase activities against doripenem, imipenem and panipenem, and IMP-1(Phe87Val) showed similar or reduced carbapenemase activities against all carbapenems tested.

Table 3.

Drug susceptibility profiles of Providencia species clinical isolates

Antibiotic MIC(μg/ml)
P. rettgeri P. stuartii
BML2496 BML2531 BML2526 BML2576 BML2537
Imipenem 16 32 512 512 >512
Meropenem 64 32 512 512 512
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Table 4.

Drug susceptibility profiles of E. coli expressing IMP-1, IMP-10, a variant of IMP-1 with an amino acid substitution (F87V) and IMP-70a

MIC(μg/ml)
antibiotic(s) E.coli DH5α
(pHSG398）		 E.coli DH5α
(pHSG398/IMP-1)		 E.coli DH5α
(pHSG398/IMP-10)b 		E.coli DH5α
(pHSG398/IMP-1(F87V))		 E.coli DH5α
(pHSG398/IMP-70)
Doripenem ≤0.06 2 8 1 4
Imipenem 0.125 1 1 1 1
Meropenem ≤0.06 4 8 2 8
Panipenem 0.125 2 2 1 2
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a Iwata S, Tada T, Hishinuma T, et al: Antimicrob Agents Chemother, 2020; 64.18)

b IMP-10 and IMP-1(V67F) amino acid arrays are the same

Table 5.

Kinetic parameters of β-lactamases IMP-1, IMP-10, a variant of IMP-1 with an amino acid substitution (F87V) and IMP-70 with substratesa

kcat/Km (μM-1・s-1)b
Substrate IMP-1 IMP-10 IMP-1(F87V) IMP-70
Doripenem 0.13 0.82 0.091 0.18
Imipenem 0.23 0.24 0.17 0.24
Meropenem 0.15 0.51 0.17 0.35
Panipenem 0.40 0.35 0.24 0.23
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a Iwata S, Tada T, Hishinuma T, et al: Antimicrob Agents Chemother, 2020; 64.18)

b Km and kcat were calculated as means ± SD from three independent experiments.

These results suggest that, in IMP-70, the Val67Phe amino acid substitution, but not the Phe87Val substitution, is important for the significantly increased carbapenemase activity against meropenem. The Val67 in IMP-1 is located at the end of “loop1”, close to the active site consisting of amino acids residues 60 to 66 (Figure 2)19). Loop1 is a major determinant for the tight binding of substrates in the active site19). A Val67Phe amino acid substitution in IMP-43, a variant of IMP-7, has been reported to increase catalytic activities against imipenem and meropenem20). Amino acid substitutions at residue 67 in IMP-1 MBLs affect their hydrolytic activity against β-lactams21). Residue 67 was reported to be important for substrate binding in VIM-type MBLs22). Residue 87 plays a crucial role in the stability of VIM-223). IMP-44, a variant of IMP-11 with two substitutions (Val67Phe and Phe87Ser), had more efficient catalytic activities against carbapenems than those of IMP-1124). These results suggest that co-occurrence of two amino acid substitutions at these two positions increase the enzymatic activities of IMP-44, whereas the Phe87Val substitution did not affect the enzymatic activities of IMP-70. The substitution of Phe87 by a polar amino acid such as Ser, but not by a hydrophobic amino acid such as Val, may affect enzymatic activities.

Figure 2.

Figure 2

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3D structure of IMP-70 MBL and amino acid sequences of IMP-1 and IMP-70 MBLs

Biological significance of two copies of blaIMP-1 in tandem

One of the P. rettgeri isolates was found to harbor two copies of blaIMP-1, in tandem on the chromosome, consisting of a repeat of the genetic structure int1Δ-blaIMP-70-qacEΔ1-sul1 (Figure 3). To confirm the presence of the two copies of blaIMP-1, sequences were amplified by PCR using a primer set targeting the two copies. Amplification resulted in a 3.5-kbp PCR product as expected based on the whole-genome sequence, indicating that this isolate of P. rettgeri harbored two tandem copies of blaIMP-1 on the chromosome. Western blotting analysis revealed that all five isolates tested produced IMP- type MBLs (Figure 4). Of these five isolates, the P. rettgeri isolates harboring two copies of blaIMP-1 produced the largest quantities of IMP-type MBL (Figure 4), indicating these two copies of blaIMP-1 produce high amounts of IMP-1 MBL.

Figure 3.

Figure 3

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Genomic environments of blaIMP-1 and blaIMP-70 in clinical isolates of P. rettgeri and P. stuartii. Genes are represented as arrows, which indicate their transcription orientations and relative lengths. MBL genes, tnp genes, and truncated genes are shown as black arrows, gray arrows, and Δ, respectively. Label orf1 represents a gene encoding a hypothetical protein, and orf2 represents a gene encoding an ATP-binding protein. This figure is a modified version of FIG 1 in reference 18.

(Iwata S, Tada T, Hishinuma T, et al: Emergence of Carbapenem-Resistant Providencia rettgeri and. Antimicrob Agents Chemother, 2020; 64.)

Figure 4.

Figure 4

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IMP-type MBL production in carbapenem-resistant clinical isolates of P. rettgeri and P. stuartii. Four clinical isolates of P. rettgeri (2496, 2526, 2531 and 2576) and one of P. stuartii (2537) were solubilized and subjected to western blot analysis using monoclonal antibodies against IMP-type MBL and GAPDH. The relative intensity of IMP-type MBL bands to GAPDH bands was calculated. This figure is a modified version of FIG 2 in reference 18. (Iwata S, Tada T, Hishinuma T, et al: Emergence of Carbapenem-Resistant Providencia rettgeri and. Antimicrob Agents Chemother, 2020; 64.)

Conclusions

The genus Providencia, belonging to the family Morganellaceae, consists of 10 species. Of these, three species, P. alcalifaciens, P. rettgeri and P. stuartii, are clinically important. P. alcalifaciens causes diarrhea by invading the intestinal mucosa, whereas P. stuartii and P. rettgeri have been found to cause hospital acquired urinary tract infections, as well as pneumonia, meningitis, endocarditis, wound infections, bloodstream infections, and travelers’ diarrhea. Clinical isolates of carbapenem- resistant P. rettgeri producing IMP-1 MBL were first identified during laboratory-based surveillance in 2000 in Japan. To date, there have been 16 reports of carbapenem-resistant P. rettgeri, eight of carbapenem-resistant P. stuartii and one of carbapenem-resistant P. vermicola, with most of these being clinical isolates.

We recently obtained four P. rettgeri isolates and one P. stuartii isolate from urine samples of five patients. All five isolates were highly resistant to carbapenems. Three isolates harbored blaIMP-70, encoding a variant of IMP-1 MBL with two amino acid substitutions, and one each harbored blaIMP-1 and blaIMP-11. Molecular analyses of these isolates strongly suggest that Providencia species become more highly resistant to carbapenems by acquisition of two copies of blaIMP-1 or by mutations in blaIMP genes that result in amino acid substitutions, such as blaIMP-70.

Funding

This study was supported by grants from Japan Society for the Promotion of Science (grants 18K07120 and 19K16652) and Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (grant number 22fk018604h702). S.I. was supported by the Training Program for Medical Students in Basic Research, Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (student number 2117016).

Author's contributions

SI collected and reviewed the presented data from previously published articles in medical journals, and drafted the manuscript. TT reviewed the data on drug-resistant genes. SO analyzed the data on biochemical experiments. TH supervised the data on drug-susceptibility profiles. MT constructed the phylogenetic tree and drafted the section of bacterial taxonomy. TT supervised this study.

Conflicts of interest statement

We have the following interests. Drs. Miho Ogawa and Masahiro Shimojima is employed by BMI Inc. There are no patents, products in development or marketed products to declare.

Acknowledgements

We thank Miho Ogawa and Masahiro Shimojima employed by BML, Inc. for screening of carbapenem-resistant clinical isolates. There are no patents, products in development, or marketed products to declare.

References

  • 1).Adeolu M, Alnajar S, Naushad S, et al. : Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int J Syst Evol Microbiol, 2016; 66: 5575-5599. [DOI] [PubMed] [Google Scholar]
  • 2).Somvanshi VS, Lang E, Sträubler B, et al. : Providencia vermicola sp. nov., isolated from infective juveniles of the entomopathogenic nematode Steinernema thermophilum. Int J Syst Evol Microbiol, 2006; 56: 629-633. [DOI] [PubMed] [Google Scholar]
  • 3).Penner JL, Hennessy JN: Application of O-serotyping in a study of Providencia rettgeri (Proteus rettgeri) isolated from human and nonhuman sources. J Clin Microbiol, 1979; 10: 834-840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4).Juneja P, Lazzaro BP: Providencia sneebia sp. nov. and Providencia burhodogranariea sp. nov., isolated from wild Drosophila melanogaster. Int J Syst Evol Microbiol, 2009; 59: 1108-1111. [DOI] [PubMed] [Google Scholar]
  • 5).Yoh M, Matsuyama J, Ohnishi M, et al. : Importance of Providencia species as a major cause of travellers' diarrhoea. J Med Microbiol, 2005; 54: 1077-1082. [DOI] [PubMed] [Google Scholar]
  • 6).O’Hara CM, Brenner FW, Miller JM: Classification, identification, and clinical significance of Proteus, Providencia, and Morganella. Clin Microbiol Rev, 2000; 13: 534-546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7).Albert MJ, Alam K, Ansaruzzaman M, et al. : Pathogenesis of Providencia alcalifaciens-induced diarrhea. Infect Immun, 1992; 60: 5017-5024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8).Albert MJ, Faruque AS, Mahalanabis D: Association of Providencia alcalifaciens with diarrhea in children. J Clin Microbiol, 1998; 36: 1433-1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9).Murata T, Iida T, Shiomi Y, et al. : A large outbreak of foodborne infection attributed to Providencia alcalifaciens. J Infect Dis, 2001; 184: 1050-1055. [DOI] [PubMed] [Google Scholar]
  • 10).Shah MM, Odoyo E, Ichinose Y: Epidemiology and pathogenesis of. Am J Trop Med Hyg, 2019; 101: 290-293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11).Washington JA, Senjem DH, Haldorson A, et al. : Nosocomially acquired bacteriuria due to Proteus rettgeri and Providencia stuartii. Am J Clin Pathol, 1973; 60: 836-838. [DOI] [PubMed] [Google Scholar]
  • 12).Krake PR, Tandon N: Infective endocarditis due to Providenca stuartii. South Med J, 2004; 97: 1022-1023. [DOI] [PubMed] [Google Scholar]
  • 13).Sharma D, Sharma P, Soni P: First case report of Providencia rettgeri neonatal sepsis. BMC Res Notes, 2017; 10: 536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14).Nordmann P, Poirel L: Epidemiology and diagnostics of carbapenem resistance in gram-negative bacteria. Clin Infect Dis, 2019; 69: S521-S528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15).Bush K, Jacoby GA: Updated functional classification of beta-lactamases. Antimicrob Agents Chemother, 2010; 54: 969-976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16).Nishio H, Komatsu M, Shibata N, et al. : Metallo-beta-lactamase-producing gram-negative bacilli: laboratory-based surveillance in cooperation with 13 clinical laboratories in the Kinki region of Japan. J Clin Microbiol, 2004; 42: 5256-5263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17).Robin F, Aggoune-Khinache N, Delmas J, et al. : Novel VIM metallo-beta-lactamase variant from clinical isolates of Enterobacteriaceae from Algeria. Antimicrob Agents Chemother, 2010; 54: 466-470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18).Iwata S, Tada T, Hishinuma T, et al. : Emergence of carbapenem-resistant Providencia rettgeri and. Antimicrob Agents Chemother, 2020; 64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19).Moali C, Anne C, Lamotte-Brasseur J, et al. : Analysis of the importance of the metallo-beta-lactamase active site loop in substrate binding and catalysis. Chem Biol, 2003; 10: 319-329. [DOI] [PubMed] [Google Scholar]
  • 20).Feng Y, Liu L, McNally A, et al. : Coexistence of Two. Antimicrob Agents Chemother, 2018; 62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21).LaCuran AE, Pegg KM, Liu EM, et al. : Elucidating the Role of Residue 67 in IMP-Type Metallo-β-Lactamase Evolution. Antimicrob Agents Chemother, 2015; 59: 7299-7307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22).Yamaguchi Y, Jin W, Matsunaga K, et al. : Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor. J Med Chem, 2007; 50: 6647-6653. [DOI] [PubMed] [Google Scholar]
  • 23).Borgianni L, Vandenameele J, Matagne A, et al. : Mutational analysis of VIM-2 reveals an essential determinant for metallo-beta-lactamase stability and folding. Antimicrob Agents Chemother, 2010; 54: 3197-3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24).Tada T, Miyoshi-Akiyama T, Shimada K, et al. : IMP-43 and IMP-44 metallo-β-lactamases with increased carbapenemase activities in multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother, 2013; 57: 4427-4432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25).Shiroto K, Ishii Y, Kimura S, et al. : Metallo-beta-lactamase IMP-1 in Providencia rettgeri from two different hospitals in Japan. J Med Microbiol, 2005; 54: 1065-1070. [DOI] [PubMed] [Google Scholar]
  • 26).Potter RF, Wallace MA, McMullen AR, et al. : bla. Clin Microbiol Infect, 2018; 24: 1019.e1015-1019.e1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27).Pathirana HNKS, Shin GW, Wimalasena SHMP, et al. : Incidence of antibiogram, antibiotic resistance genes and class 1 and 2 integrons in tribe Proteeae with IMP27 gene for the first time in Providencia sp. isolated from pet turtles. Lett Appl Microbiol, 2018; 67: 620-627. [DOI] [PubMed] [Google Scholar]
  • 28).Gefen-Halevi S, Hindiyeh MY, Ben-David D, et al. : Isolation of genetically unrelated bla(NDM-1)-positive Providencia rettgeri strains in Israel. J Clin Microbiol, 2013; 51: 1642-1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29).Tada T, Miyoshi-Akiyama T, Dahal RK, et al. : NDM-1 Metallo-β-Lactamase and ArmA 16S rRNA methylase producing Providencia rettgeri clinical isolates in Nepal. BMC Infect Dis, 2014; 14: 56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30).Barrios H, Garza-Ramos U, Reyna-Flores F, et al. : Isolation of carbapenem-resistant NDM-1-positive Providencia rettgeri in Mexico. J Antimicrob Chemother, 2013; 68: 1934-1936. [DOI] [PubMed] [Google Scholar]
  • 31).Zhou G, Guo S, Luo Y, et al. : NDM-1-producing strains, family Enterobacteriaceae, in hospital, Beijing, China. Emerg Infect Dis, 2014; 20: 340-342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32).Pfeifer Y, Trifonova A, Pietsch M, et al. : Clonal Transmission of Gram-Negative Bacteria with Carbapenemases NDM-1, VIM-1, and OXA-23/72 in a Bulgarian Hospital. Microb Drug Resist, 2017; 23: 301-307. [DOI] [PubMed] [Google Scholar]
  • 33).Carvalho-Assef AP, Pereira PS, Albano RM, et al. : Isolation of NDM-producing Providencia rettgeri in Brazil. J Antimicrob Chemother, 2013; 68: 2956-2957. [DOI] [PubMed] [Google Scholar]
  • 34).Piza-Buitrago A, Rincón V, Donato J, et al. : Genome-based characterization of two Colombian clinical Providencia rettgeri isolates co-harboring NDM-1, VIM-2, and other β-lactamases. BMC Microbiol, 2020; 20: 345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35).Ntshobeni NB, Allam M, Ismail A, et al. : Draft Genome Sequence of Providencia rettgeri APW139_S1, an NDM-18-Producing Clinical Strain Originating from Hospital Effluent in South Africa. Microbiol Resour Announc, 2019; 8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36).McGann P, Hang J, Clifford RJ, et al. : Complete sequence of a novel 178-kilobase plasmid carrying bla(NDM-1) in a Providencia stuartii strain isolated in Afghanistan. Antimicrob Agents Chemother, 2012; 56: 1673-1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37).Lezameta L, Cuicapuza D, Dávila-Barclay A, et al. : Draft Genome Sequence of a New Delhi Metallo-β-Lactamase (NDM-1)-Producing Providencia stuartii Strain Isolated in Lima, Peru. Microbiol Resour Announc, 2020; 9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38).Douka E, Perivolioti E, Kraniotaki E, et al. : Emergence of a pandrug-resistant VIM-1-producing Providencia stuartii clonal strain causing an outbreak in a Greek intensive care unit. Int J Antimicrob Agents, 2015; 45: 533-536. [DOI] [PubMed] [Google Scholar]
  • 39).Drieux L, Decré D, Frangeul L, et al. : Complete nucleotide sequence of the large conjugative pTC2 multireplicon plasmid encoding the VIM-1 metallo-β-lactamase. J Antimicrob Chemother, 2013; 68: 97-100. [DOI] [PubMed] [Google Scholar]
  • 40).Galani L, Galani I, Souli M, et al. : Nosocomial dissemination of Providencia stuartii isolates producing extended-spectrum β-lactamases VEB-1 and SHV-5, metallo-β-lactamase VIM-1, and RNA methylase RmtB. J Glob Antimicrob Resist, 2013; 1: 115-116. [DOI] [PubMed] [Google Scholar]
  • 41).Lee HW, Kang HY, Shin KS, et al. : Multidrug-resistant Providencia isolates carrying blaPER-1, blaVIM-2, and armA. J Microbiol, 2007; 45: 272-274. [PubMed] [Google Scholar]
  • 42).Lupande-Mwenebitu D, Khedher MB, Khabthani S, et al: First genome description of Microorganisms, 2021; 9. [DOI] [PMC free article] [PubMed]

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