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Volume 167, Issue 10

The MpsB protein contributes to both the toxicity and immune evasion capacity of Open Access

Abstract

Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen . By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance-associated genes, , and . Detailed analysis of an MpsB mutant supports its previous association with the slow growing small colony variant (SCV) phenotype of , and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion for the ability of to cause disease, we believe that these findings explain the role of the gene as a mortality-associated locus during human disease.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): mpsB , serum survival , small colony variants and Staphylococcus aureus
Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council
    • Principle Award Recipient: RuthC Massey
  • Wellcome Trust (Award 212258/Z/18/Z)
    • Principle Award Recipient: RuthC Massey
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-10-07
2024-12-05
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References

  1. Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339:520–532 [View Article]
     [Google Scholar]
  2. Gordon RJ, Lowy FD. Pathogenesis of methicillin‐resistant Staphylococcus aureus infection. Clin Infect Dis 2008; 46:S350–9 [View Article] [PubMed]
     [Google Scholar]
  3. van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL et al. Predictors of Mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev 2012; 25:362–386 [View Article] [PubMed]
     [Google Scholar]
  4. Lamagni TL, Potz N, Powell D, Pebody R, Wilson J et al. Mortality in patients with meticillin-resistant Staphylococcus aureus bacteraemia, England 2004–2005. J Hosp Infect 2011; 77: [View Article]
     [Google Scholar]
  5. Kang C-I, Song J-H, KS K, Chung DR, Peck KR. Clinical features and outcome of Staphylococcus aureus infection in elderly versus younger adult patients. Int J Infect Dis 2011; 15: [View Article]
     [Google Scholar]
  6. Recker M, Laabei M, Toleman MS, Reuter S, Saunderson RB et al. Clonal differences in Staphylococcus aureus bacteraemia-associated mortality. Nat Microbiol 2017; 2:1381–1388 [View Article] [PubMed]
     [Google Scholar]
  7. Fan S-H, Ebner P, Reichert S, Hertlein T, Zabel S et al. MpsAB is important for Staphylococcus aureus virulence and growth at atmospheric CO2 levels. Nat Commun 2019; 10:3627 [View Article]
     [Google Scholar]
  8. Mayer S, Steffen W, Steuber J, Götz F. The Staphylococcus aureus NuoL-like protein mpsa contributes to the generation of membrane potential. J Bacteriol 2015; 197:794–806 [View Article] [PubMed]
     [Google Scholar]
  9. Corrigan RM, Foster TJ. An improved tetracycline-inducible expression vector for Staphylococcus aureus. Plasmid 2009; 61:126–129 [View Article] [PubMed]
     [Google Scholar]
  10. Andrews JM. Determination of minimum inhibitory concentrations. J Antimicrob Chemother 2001; 48: [View Article]
     [Google Scholar]
  11. Fey PD, Endres JL, Yajjala VK, Widhelm TJ, Boissy RJ et al. A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes. mBio 2013; 4:e00537 [View Article] [PubMed]
     [Google Scholar]
  12. Duggan S, Laabei M, Alnahari AA, O’Brien EC, Lacey KA. Small membrane stabilizing protein critical to the pathogenicity of staphylococcus aureus. Infect Immun 202088–e00162 [View Article] [PubMed]
     [Google Scholar]
  13. Morikawa K, Maruyama A, Inose Y, Higashide M, Hayashi H et al. Overexpression of sigma factor, ςB, urges Staphylococcus aureus to thicken the cell wall and to resist β-Lactams. Biochem Biophys Res Commun 2001; 288:385–389 [View Article] [PubMed]
     [Google Scholar]
  14. Stevens E, Laabei M, Gardner S, Somerville GA, Massey RC. Cytolytic toxin production by Staphylococcus aureus is dependent upon the activity of the protoheme IX farnesyltransferase. Sci Rep 2017; 7:13744 [View Article] [PubMed]
     [Google Scholar]
  15. Bunting JR, Phan TV, Kamali E, Dowben RM. Fluorescent cationic probes of mitochondria. Metrics and mechanism of interaction. Biophys J 1989; 56: [View Article]
     [Google Scholar]
  16. Kasianowicz J, Benz R, McLaughlin S. The kinetic mechanism by which CCCP (carbonyl cyanidem-Chlorophenylhydrazone) transports protons across membranes. J Membr Biol 1984; 82:179–190 [View Article] [PubMed]
     [Google Scholar]
  17. Massey RC, Buckling A, Peacock SJ. Phenotypic switching of antibiotic resistance circumvents permanent costs in Staphylococcus aureus. Curr Biol 2001; 11:1810–1814 [View Article] [PubMed]
     [Google Scholar]
  18. Sadowska B, Bonar A, Eiff C, Proctor RA, Chmiela M et al. Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants. FEMS Immunology & Medical Microbiology 2002; 32: [View Article]
     [Google Scholar]
  19. Gläser R, Becker K, von Eiff C, Meyer-Hoffert U, Harder J. Decreased susceptibility of Staphylococcus aureus small-colony variants toward human antimicrobial peptides. J Invest Dermatol 2014; 134: [View Article]
     [Google Scholar]
  20. McNamara PJ, Proctor RA. Staphylococcus aureus small colony variants, electron transport and persistent infections. Int J Antimicrob Agents 200014117–122 [View Article] [PubMed]
     [Google Scholar]
  21. Laabei M, Uhlemann A-C, Lowy FD, Austin ED, Yokoyama M et al. Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus. PLoS Biol 2015; 13:e1002229 [View Article] [PubMed]
     [Google Scholar]
  22. von Eiff C, Heilmann C, Proctor RA, Woltz C, Peters G et al. A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. J Bacteriol 1997; 179:15 [View Article]
     [Google Scholar]
  23. Peng HL, Novick RP, Kreiswirth B, Kornblum J, Schlievert P. Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol 1988; 170:4365–4372 [View Article] [PubMed]
     [Google Scholar]
  24. Yamada Y, Shiota S, Mizushima T, Kuroda T, Tsuchiya T. Functional gene cloning and characterization of MDEA, a multidrug efflux pump from Staphylococcus aureus. Biol Pharm Bull 2006; 29:801–804 [View Article]
     [Google Scholar]
  25. Huang J, O’Toole PW, Shen W, Amrine-Madsen H, Jiang X et al. Novel Chromosomally Encoded Multidrug Efflux Transporter MdeA in Staphylococcus aureus. Antimicrob Agents Chemother 2004; 48:909–917 [View Article] [PubMed]
     [Google Scholar]
  26. Cameron DR, Jiang J-. H, Kostoulias X, Foxwell DJ, Peleg AY. Vancomycin susceptibility in methicillin-resistant Staphylococcus aureus is mediated by YycHI activation of the WalRK essential two-component regulatory system. Sci Rep 2016; 6:30823 [View Article] [PubMed]
     [Google Scholar]
  27. Sutton JAF, Carnell OT, Lafage L, Gray J, Biboy J. Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction. PLoS Pathog 2021e1009468 [PubMed]
     [Google Scholar]
  28. Peschel A. How do bacteria resist human antimicrobial peptides?. Trends Microbiol 200210179–186 [View Article] [PubMed]
     [Google Scholar]
  29. Psychogios N, Hau DD, Peng J, Guo AC, Mandal R. The human serum metabolome. PLoS ONE 2011e16957 [PubMed]
     [Google Scholar]
/content/journal/micro/10.1099/mic.0.001096
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The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus
Microbiology 167, 001096 (2021); https://doi.org/10.1099/mic.0.001096
/content/journal/micro/10.1099/mic.0.001096
/content/journal/micro/10.1099/mic.0.001096
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