Table 1.
Characteristics of the Included Studies.
| First Author/Year/Ref | Type of Study | Cohort | Aims | Finding |
|---|---|---|---|---|
| Lockhart et al. (2008) Circulation [46] |
Human RCT Single Center (USA) |
290 pts Brushing Gro 98 vs. Extraction-Amoxicillin 96 vs. Extraction-Placebo 96 |
To compare the incidence, duration, nature, and magnitude of IE-related bacteremia from single-tooth extraction and toothbrushing. To determine the impact of amoxicillin prophylaxis on single-tooth extraction. |
Amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction. Toothbrushing may be a greater threat for individuals at risk for infective endocarditis. |
| Mancini et al. (2018) Virulence [49] |
Animal (Switzerland pilot) |
Rat with catheter-induced aortic vegetations | To investigate the role of Coa and vWbp in IE initiation | Coa does not support the initial colonization of IE (in L. lactis). vWbp contributes to the initiation of IE (in L. lactis) however is marginal in the presence of ClfA. |
| Reguiero et al. (2019) Circ. Cardiovasc. Interv. [51] |
Human Comparative Multicenter (Canada pilot) | 245 pts SEV 115 vs. BEV 130 |
To determine the incidence, clinical characteristics, and outcomes of patients with IE post-TAVR | IE post-TAVR did not reveal early or late mortality |
| Rodríguez-Vidigal et al. (2019) Enferm. Infecc. Microbiol. Clin. [52] |
Human Observational Retrospective (Spain) |
200 pts with TAVI | To evaluate single-centre experience of incidence, mortality, and associated factors of IE after TAVI. | Incidence of IE post-TAVI greater than other series. |
| Di Carluccio et al. (2021) RSC Chem. Biol. [55] |
Human Multicenter (Italy pilot) |
Collected anatomical specimen | To evaluate the mechanism of interaction of SLBR-B and SLBR-H from S. gordonii in causing IE | Streptococcal Siglec-like adhesins spark the development of tailored synthetic inhibitors and therapeutics specific for Streptococcal adhesins to counteract IE. No impairment of the interplay between Siglecs and glycans. |
| Manukumar et al. (2017) Sci. Rep. [56] |
Human Single Center (India) |
Collected blood draws | To characterize MRSA strain using MALDI-Biotyper multiplex PCR to distinguish between MRSA and MSSA. To screen PCR-SSCP | PCR-SSCP technique for rapid detection of MSSA and MRSA strains was developed |
| Mempel et al. (2002) Br. J. Dermatol. [57] |
Human Single Center (Germany) |
† S. aureus DU 5720 vs. S. aureus DU 8325-4 vs. S. aureus DU 5883 |
To investigate haemolysin-independent virulence in human keratinocytes. | Staphylococcal invasion of human keratinocytes independently of alpha- and beta-hemolysins, leads to necrotic and apoptotic cell damage. |
| Nakagawa et al. (2017) Cell Host Microbe J. [58] |
Animal Multicenter Center (Japan pilot) |
Murine epicutaneous infection model | To evaluate how S. aureus trigger inflammation | Increased production of IL-1α, IL-36α and Il 17 via IL-1R and IL-36R. Increased γδ T cells, ILC3 and neutrophil. Keratinocyte * Myd88 signaling in response to S. aureus PSMα drives an IL-17-mediated skin inflammatory response to epicutaneous S. aureus infection. |
| Schwarz et al. (2021) Virulence [63] |
Human in vitro and in vivo Multicenter (Germany) |
34 S. aureus
Pts with S. aureus endocarditis vs. healthy individuals |
To evaluate pathomechanisms in the induction of IE | in vitro assays did not correlate with the severity of IE. S. aureus isolates differed in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response |
| Malachowa et al. (2011) PLoS ONE [64] |
Human/Animal Single center (USA) |
S. aureus LAC vs. S. aureus LACΔhlgABC |
To study the S. aureus USA300 transcriptome | Limited contribution of any single two-component leukotoxin lukS-PV and lukF-PV to USA300 immune evasion and virulence. |
| Alonso et al. (2013) Nature [65] |
Animal Single center (USA) |
CCR5-deficient mice | To study activity of S. aureus leukotoxin ED (LukED) | CCR5-deficient mice are resistant to lethal S. aureus infection |
| Kim et al. (2010) J. Exp. Med. [71] |
Animal Single center (USA) |
λ Mice with SpA (KKAA) | To study S. aureus protective immunity. | SpA (KKAA) immunization enabled MRSA-challenged mice to organize antibody responses to many different staphylococcal antigens. |
| Becker et al. (2014) Proc. Natl. Acad. Sci. USA [72] |
In vitro Single center (USA) |
S. aureus Newman cultures | To demonstrate that SpA is released with murein tetrapeptide-tetraglycyl [L-Ala-D-iGln-(SpA-Gly5) L-Lys-D-Ala-Gly4] linked to its C-terminal threonyl | SpA, a B cell superantigen, is released with peptidoglycan linked to its C terminus. Murein hydrolases cleave the anchor structure of released SpA to modify host immune responses. |
| Zhang et al. (2015) Infect. Immun. [84] |
Animal Single center (China) |
Mice SaEsxA and SaEsxB vs. Mice rSaEsxA and rSaEsxB |
To investigate SaEsxA and SaEsxB, as possible targets for a vaccine. | SaEsxA and SaEsxB are effective toward Th1 and Th17 candidate antigens. |
| Brady et al. (2013) PLoS ONE [85] |
Animal Single center (USA) |
Mice HlaH35L vs. Control vs. Prosthetic implant model of chronic biofilm |
To evaluate the ability of one S. aureus vaccine antigen to protect in three mouse models of infection | Vaccines may confer protection against one form of S. aureus disease without conferring protection against other disease presentations |
| Zhang et al. (2018) mBio [86] |
Animal Multicenter (USA pilot) |
C57BL/6 mice | To study the role of adaptive immunity induced by an S. aureus vaccine in protection against S. aureus bacteremia | Multipronged humoral and cellular (B-cell, Th1, Th17) responses to S. aureus antigens may be critical to achieve effective and comprehensive immune defense |
| Yu et al. (2018) Sci. Rep. [87] |
Animal Single center (China) |
Mouse peritonitis model | To evaluate the humoral immune response and CD4+ T cell-mediated immune responses | The MntC-specific antibodies and MntC-specific Th17 cells play cooperative roles in the prevention of S. aureus infection. |
Abbreviations: BEV, balloon-expandable valve; C57BL/6, C57 black 6; CCR5, C-C chemokine receptor type 5; ClfA, clumping factor A; Coa, plasma-clotting factors staphylocoagulase; DU, S. aureus mutant; IE, infective endocarditis; γδ T cells, Gamma delta T cells; IL, interleukine; ILC3, group 3 innate lymphoid cells; HaCaT, aneuploid immortal keratinocyte cell; LAC, wild-type USA300 strain; LACΔhlgABC, hlgABC-deletion strain; L. lactis, Lactococcus lactis; lukS/F-PV, leukotoxin S/F-Panton-Valentine; LukED, S. aureus leukotoxin ED; MntC, S. aureus manganese transport protein C; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible S. aureus; PCR, protein chain reaction; PCR-SSCP, PCR-coupled single strand conformation polymorphism; PSM, phenol-soluble modulin α; Pt, patient; PVL, Panton-Valentine Leukocidin; rSaEsx, recombinant; SaEsx, S. aureus Esx; SEV, self-expanding valve; SLBR, Siglec-like binding region; SpA, staphylococcal protein A; TAVI, transcatheter aortic valve implantation; Th17, T helper 17 cells; TSB, trypticase soy broth. † S. aureus mutant DU 5720 alpha-haemolysin, beta-haemolysin double-negative; S. aureus mutant virulent strain DU 8325-4; S. aureus variant DU 5883 isogenic fibronectin-binding protein A/B-negative. * Myd88, keratinocyte-specific deletion of the IL-1R and IL-36R; λ variant KKAA staphylococcal protein A.