GBD 2021 Antimicrobial Resistance Collaborators Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet 404, 1199–1226 (2024).
Osterloh, A. Vaccination against bacterial infections: challenges, progress, and new approaches with a focus on intracellular bacteria. Vaccines 10, 751 (2022).
Da Costa, R. M., Rooke, J. L., Wells, T. J., Cunningham, A. F. & Henderson, I. R. Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections. NPJ Vaccines 9, 159 (2024).
Shinefield, H. R. & Black, S. Efficacy of pneumococcal conjugate vaccines in large scale field trials. Pediatr. Infect. Dis. J. 19, 394–397 (2000).
Goldblatt, D. Conjugate vaccines. Clin. Exp. Immunol. 119, 1–3 (2000).
Clegg, J. et al. Staphylococcus aureus vaccine research and development: the past, present and future, including novel therapeutic strategies. Front. Immunol. 12, 705360 (2021).
Gallego Rodriguez, A. et al. Risk factors for mortality and complications in peripheral venous catheter-associated Staphylococcus aureus bacteraemia: a large multicentre cohort study. J. Hosp. Infect. 152, 13–20 (2024).
van Hal, S. J. et al. Predictors of mortality in Staphylococcus aureus bacteremia. Clin. Microbiol. Rev. 25, 362–386 (2012).
Brown, A. F. et al. Memory Th1 cells are protective in invasive Staphylococcus aureus infection. PLoS Pathog. 11, e1005226 (2015).
Braverman, J. et al. Staphylococcus aureus specific lung resident memory CD4+ Th1 cells attenuate the severity of influenza virus induced secondary bacterial pneumonia. Mucosal. Immunol. 15, 783–796 (2022).
Braverman, J., Monk, I. R., Zhang, H., Stinear, T. P. & Wakim, L. M. Polyclonal but not monoclonal circulating memory CD4+ T cells attenuate the severity of Staphylococcus aureus bacteremia. Front. Immunol. 15, 1417220 (2024).
Minegishi, Y. et al. Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J. Exp. Med. 206, 1291–1301 (2009).
Utay, N. S. et al. MRSA infections in HIV-infected people are associated with decreased MRSA-specific Th1 immunity. PLoS Pathog. 12, e1005580 (2016).
Fuertes Marraco, S. A. et al. Novel murine dendritic cell lines: a powerful auxiliary tool for dendritic cell research. Front. Immunol. 3, 331 (2012).
Purcell, A. W., Ramarathinam, S. H. & Ternette, N. Mass spectrometry-based identification of MHC-bound peptides for immunopeptidomics. Nat. Protoc. 14, 1687–1707 (2019).
Wang, X. et al. Conserved moonlighting protein pyruvate dehydrogenase induces robust protection against Staphylococcus aureus infection. Proc. Natl Acad. Sci. USA 121, e2321939121 (2024).
Hassanzadeh, H. et al. Efficacy of a 4-antigen Staphylococcus aureus vaccine in spinal surgery: the STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) randomized clinical trial. Clin. Infect. Dis. 77, 312–320 (2023).
Zuhlke, D. et al. Costs of life—dynamics of the protein inventory of Staphylococcus aureus during anaerobiosis. Sci. Rep. 6, 28172 (2016).
Pizzolla, A. et al. Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci. Immunol. 2, eaam6970 (2017).
Wakim, L. M., Smith, J., Caminschi, I., Lahoud, M. H. & Villadangos, J. A. Antibody-targeted vaccination to lung dendritic cells generates tissue-resident memory CD8 T cells that are highly protective against influenza virus infection. Mucosal Immunol. 8, 1060–1071 (2015).
Chen, Z. et al. Humanized transgenic mice expressing HLA DR4-DQ3 haplotype: reconstitution of phenotype and HLA-restricted T-cell responses. Tissue Antigens 68, 210–219 (2006).
Greenbaum, J. et al. Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes. Immunogenetics 63, 325–335 (2011).
Sette, A. & Rappuoli, R. Reverse vaccinology: developing vaccines in the era of genomics. Immunity 33, 530–541 (2010).
Lacey, K. A. et al. The Staphylococcus aureus cell wall-anchored protein clumping factor A is an important T cell antigen. Infect. Immun. 85, e00549-17 (2017).
Armentrout, E. I., Liu, G. Y. & Martins, G. A. T cell immunity and the quest for protective vaccines against Staphylococcus aureus infection. Microorganisms 8, 1936 (2020).
Bennek, E. et al. Subcellular antigen localization in commensal E. coli is critical for T cell activation and induction of specific tolerance. Mucosal Immunol. 12, 97–107 (2019).
Cummings, L. A., Barrett, S. L., Wilkerson, W. D., Fellnerova, I. & Cookson, B. T. FliC-specific CD4+ T cell responses are restricted by bacterial regulation of antigen expression. J. Immunol. 174, 7929–7938 (2005).
Chen, Y. E. et al. Engineered skin bacteria induce antitumor T cell responses against melanoma. Science 380, 203–210 (2023).
Strzalka, A. et al. The role of two major nucleoid-associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation. Microb. Cell Fact. 23, 275 (2024).
Kim, D. H. et al. β-Arm flexibility of HU from Staphylococcus aureus dictates the DNA-binding and recognition mechanism. Acta Crystallogr. D 70, 3273–3289 (2014).
Letran, S. E. et al. TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. Eur. J. Immunol. 41, 29–38 (2011).
Zheng, Y. et al. Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe 30, 301–313.e9 (2022).
Cogen, A. L. et al. Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. PLoS ONE 5, e8557 (2010).
Nakatsuji, T., Fenical, W. & Gallo, R. L. Response to comment on ‘A commensal strain of Staphylococcus epidermidis protects against skin neoplasia’ by Nakatsuji et al. Sci. Adv. 5, eaay5611 (2019).
Brown, M. M. & Horswill, A. R. Staphylococcus epidermidis—skin friend or foe?. PLoS Pathog. 16, e1009026 (2020).
Hendriks, A. et al. Staphylococcus aureus-specific tissue-resident memory CD4+ T cells are abundant in healthy human skin. Front. Immunol. 12, 642711 (2021).
Colque-Navarro, P., Jacobsson, G., Andersson, R., Flock, J. I. & Mollby, R. Levels of antibody against 11 Staphylococcus aureus antigens in a healthy population. Clin. Vaccine Immunol. 17, 1117–1123 (2010).
Wu, Y. et al. Prevalence of IgG and neutralizing antibodies against Staphylococcus aureus alpha-toxin in healthy human subjects and diverse patient populations. Infect. Immun. 86, e00671-17 (2018).
Wertheim, H. F. et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 364, 703–705 (2004).
Weckel, A. et al. Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup. Immunity 56, 1239–1254.e7 (2023).
Wang, S. et al. MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity 43, 289–303 (2015).
Belkaid, Y., Bouladoux, N. & Hand, T. W. Effector and memory T cell responses to commensal bacteria. Trends Immunol. 34, 299–306 (2013).
Augustyniak, D., Majkowska-Skrobek, G., Roszkowiak, J. & Dorotkiewicz-Jach, A. Defensive and offensive cross-reactive antibodies elicited by pathogens: the good, the bad and the ugly. Curr. Med. Chem. 24, 4002–4037 (2017).
Conway, J. et al. Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip. Antimicrob. Agents Chemother. 68, e0065524 (2024).
Burke, Z. D. C. et al. Monoclonal antibody disrupts biofilm structure and restores antibiotic susceptibility in an orthopedic implant infection model. Antibiotics 12, 1490 (2023).
Xiong, Y. Q. et al. A human biofilm-disrupting monoclonal antibody potentiates antibiotic efficacy in rodent models of both Staphylococcus aureus and Acinetobacter baumannii infections. Antimicrob. Agents Chemother. 61, e00904–e00917 (2017).
Kolata, J. B. et al. The fall of a dogma? Unexpected high T-cell memory response to Staphylococcus aureus in humans. J. Infect. Dis. 212, 830–838 (2015).
Clegg, J. et al. Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects—a hurdle for vaccination?. Front. Immunol. 15, 1500696 (2024).
Sanchez, M. et al. O-acetylation of peptidoglycan limits helper T cell priming and permits Staphylococcus aureus reinfection. Cell Host Microbe 22, 543–551.e4 (2017).
Kelly, A. M. et al. IL-10 inhibition during immunization improves vaccine-induced protection against Staphylococcus aureus infection. JCI Insight 9, e178216 (2024).
Tsai, C. M. et al. Non-protective immune imprint underlies failure of Staphylococcus aureus IsdB vaccine. Cell Host Microbe 30, 1163–1172.e6 (2022).
Hajam, I. A. et al. Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses. Nat. Commun. 15, 10335 (2024).
Si, Y. et al. Inhibition of protective immunity against Staphylococcus aureus infection by MHC-restricted immunodominance is overcome by vaccination. Sci. Adv. 6, eaaw7713 (2020).
Yeaman, M. R. et al. Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection. Proc. Natl Acad. Sci. USA 111, E5555–E5563 (2014).
Bedoui, S. et al. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat. Immunol. 10, 488–495 (2009).
Ge, C. et al. Neutrophils play an ongoing role in preventing bacterial pneumonia by blocking the dissemination of Staphylococcus aureus from the upper to the lower airways. Immunol. Cell Biol. 98, 577–594 (2020).
Short, K. R. et al. Using bioluminescent imaging to investigate synergism between Streptococcus pneumoniae and influenza A virus in infant mice. J. Vis. Exp. 14, 2357 (2011).
Monk, I. R. & Stinear, T. P. From cloning to mutant in 5 days: rapid allelic exchange in Staphylococcus aureus. Access Microbiol. 3, 000193 (2021).
Pandey, K., Ramarathinam, S. H. & Purcell, A. W. Isolation of HLA bound peptides by immunoaffinity capture and identification by mass spectrometry. Curr. Protoc. 1, e92 (2021).
Escher, C. et al. Using iRT, a normalized retention time for more targeted measurement of peptides. Proteomics 12, 1111–1121 (2012).
Reynisson, B. et al. Improved prediction of MHC II antigen presentation through integration and motif deconvolution of mass spectrometry MHC eluted ligand data. J. Proteome Res. 19, 2304–2315 (2020).
Yu, N. Y. et al. PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 26, 1608–1615 (2010).
Paul, S. et al. Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes. J. Immunol. Methods 422, 28–34 (2015).
Giulieri, S. G. et al. A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteremia. Cell Rep. 42, 113069 (2023).
Tonkin-Hill, G. et al. Producing polished prokaryotic pangenomes with the Panaroo pipeline. Genome Biol. 21, 180 (2020).
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069 (2014).
Sievers, F. & Higgins, D. G. Clustal Omega for making accurate alignments of many protein sequences. Protein Sci. 27, 135–145 (2018).
Bonn, F. et al. Global analysis of the impact of linezolid onto virulence factor production in S. aureus USA300. Int. J. Med. Microbiol. 306, 131–140 (2016).
Loh, T. J. et al. The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4. Nat. Commun. 15, 6201 (2024).
Brochet, X., Lefranc, M. P. & Giudicelli, V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 36, W503–W508 (2008).
Dash, P. et al. Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature 547, 89–93 (2017).
Lee, J. Y. H. et al. Mining the methylome reveals extensive diversity in Staphylococcus epidermidis restriction modification. MBio 10, 19 (2019).
Zheng, M. Z. M. et al. Single-cycle influenza virus vaccine generates lung CD8+ Trm that cross-react against viral variants and subvert virus escape mutants. Sci. Adv. 9, eadg3469 (2023).


















Leave a Reply