Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality and a great concern for public health. The CC30 MRSA lineage is especially notorious for causing bloodstream infections with complications such as seeding into organs. In our study, we show that this lineage produces an attenuated form of a key S. aureus toxin with decreased pro-inflammatory features. Our results suggest that attenuation of this toxin allows the bacteria to evade recognition and subsequent elimination by host defenses, thereby increasing pathogen success during blood infection.
Vyšlo v časopise:
Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004298
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004298
Souhrn
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality and a great concern for public health. The CC30 MRSA lineage is especially notorious for causing bloodstream infections with complications such as seeding into organs. In our study, we show that this lineage produces an attenuated form of a key S. aureus toxin with decreased pro-inflammatory features. Our results suggest that attenuation of this toxin allows the bacteria to evade recognition and subsequent elimination by host defenses, thereby increasing pathogen success during blood infection.
Zdroje
1. LowyFD (1998) Staphylococcus aureus infections. N Engl J Med 339: 520–532.
2. FosterTJ (2005) Immune evasion by staphylococci. Nat Rev Microbiol 3: 948–958.
3. OttoM (2012) MRSA virulence and spread. Cell Microbiol 14: 1513–1521.
4. OttoM (2013) Community-associated MRSA: what makes them special? Int J Med Microbiol 303: 324–330.
5. CoxRA, ConquestC, MallaghanC, MarplesRR (1995) A major outbreak of methicillin-resistant Staphylococcus aureus caused by a new phage-type (EMRSA-16). J Hosp Infect 29: 87–106.
6. JohnsonAP, AuckenHM, CavendishS, GannerM, WaleMC, et al. (2001) Dominance of EMRSA-15 and -16 among MRSA causing nosocomial bacteraemia in the UK: analysis of isolates from the European Antimicrobial Resistance Surveillance System (EARSS). J Antimicrob Chemother 48: 143–144.
7. McAdamPR, TempletonKE, EdwardsGF, HoldenMT, FeilEJ, et al. (2012) Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci U S A 109: 9107–9112.
8. FowlerVGJr, NelsonCL, McIntyreLM, KreiswirthBN, MonkA, et al. (2007) Potential associations between hematogenous complications and bacterial genotype in Staphylococcus aureus infection. J Infect Dis 196: 738–747.
9. DeLeoFR, KennedyAD, ChenL, Bubeck WardenburgJ, KobayashiSD, et al. (2011) Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc Natl Acad Sci U S A 108: 18091–18096.
10. PeschelA, OttoM (2013) Phenol-soluble modulins and staphylococcal infection. Nat Rev Microbiol 11: 667–673.
11. WangR, BraughtonKR, KretschmerD, BachTH, QueckSY, et al. (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13: 1510–1514.
12. CheungGY, DuongAC, OttoM (2012) Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble modulins: implications for diagnosis and pathogenesis. Microbes Infect 14: 380–386.
13. RasigadeJP, Trouillet-AssantS, FerryT, DiepBA, SapinA, et al. (2013) PSMs of hypervirulent Staphylococcus aureus act as intracellular toxins that kill infected osteoblasts. PLoS One 8: e63176.
14. KretschmerD, GleskeAK, RautenbergM, WangR, KoberleM, et al. (2010) Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus. Cell Host Microbe 7: 463–473.
15. CheungGY, JooHS, ChatterjeeSS, OttoM (2013) Phenol-soluble modulins - critical determinants of staphylococcal virulence. FEMS Microbiol Rev doi: 10.1111/1574-6976.12057. [Epub ahead of print]
16. GravesSF, KobayashiSD, BraughtonKR, WhitneyAR, SturdevantDE, et al. (2012) Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity. J Leukoc Biol 92: 361–374.
17. JooHS, OttoM (2014) The isolation and analysis of phenol-soluble modulins of Staphylococcus epidermidis. Methods Mol Biol 1106: 93–100.
18. HoldenMT, FeilEJ, LindsayJA, PeacockSJ, DayNP, et al. (2004) Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci U S A 101: 9786–9791.
19. QueckSY, Jameson-LeeM, VillaruzAE, BachTH, KhanBA, et al. (2008) RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus. Mol Cell 32: 150–158.
20. TraberKE, LeeE, BensonS, CorriganR, CanteraM, et al. (2008) agr function in clinical Staphylococcus aureus isolates. Microbiology 154: 2265–2274.
21. NovickRP, RossHF, ProjanSJ, KornblumJ, KreiswirthB, et al. (1993) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12: 3967–3975.
22. JooHS, CheungGY, OttoM (2011) Antimicrobial activity of community-associated methicillin-resistant Staphylococcus aureus is caused by phenol-soluble modulin derivatives. J Biol Chem 286: 8933–8940.
23. PratC, BestebroerJ, de HaasCJ, van StrijpJA, van KesselKP (2006) A new staphylococcal anti-inflammatory protein that antagonizes the formyl peptide receptor-like 1. J Immunol 177: 8017–8026.
24. de HaasCJ, VeldkampKE, PeschelA, WeerkampF, Van WamelWJ, et al. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med 199: 687–695.
25. DuongAC, CheungGY, OttoM (2012) Interaction of phenol-soluble modulins with phosphatidylcholine vesicles. Pathogens 1: 3–11.
26. KobayashiSD, MalachowaN, WhitneyAR, BraughtonKR, GardnerDJ, et al. (2011) Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J Infect Dis 204: 937–941.
27. SurewaardBG, de HaasCJ, VervoortF, RigbyKM, DeLeoFR, et al. (2013) Staphylococcal alpha-phenol soluble modulins contribute to neutrophil lysis after phagocytosis. Cell Microbiol 15: 1427–1437.
28. SpaanAN, SurewaardBG, NijlandR, van StrijpJA (2013) Neutrophils versus Staphylococcus aureus: a biological tug of war. Annu Rev Microbiol 67: 629–650.
29. HolzingerD, GieldonL, MysoreV, NippeN, TaxmanDJ, et al. (2012) Staphylococcus aureus Panton-Valentine leukocidin induces an inflammatory response in human phagocytes via the NLRP3 inflammasome. J Leukoc Biol 92: 1069–1081.
30. YoongP, PierGB (2012) Immune-activating properties of Panton-Valentine leukocidin improve the outcome in a model of methicillin-resistant Staphylococcus aureus pneumonia. Infect Immun 80: 2894–2904.
31. HermosCR, YoongP, PierGB (2010) High levels of antibody to Panton-Valentine leukocidin are not associated with resistance to Staphylococcus aureus-associated skin and soft-tissue infection. Clin Infect Dis 51: 1138–1146.
32. YoongP, PierGB (2010) Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection. Proc Natl Acad Sci U S A 107: 2241–2246.
33. FowlerVGJr, SakoulasG, McIntyreLM, MekaVG, ArbeitRD, et al. (2004) Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J Infect Dis 190: 1140–1149.
34. PaulanderW, Nissen VarmingA, BaekKT, HaaberJ, FreesD, et al. (2013) Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus. mBio 3: e00459-00412.
35. CheungGY, KretschmerD, QueckSY, JooHS, WangR, et al. (2014) Insight into structure-function relationship in phenol-soluble modulins using an alanine screen of the phenol-soluble modulin (PSM) alpha3 peptide. FASEB J 28: 153–161.
36. ChatterjeeSS, JooHS, DuongAC, DieringerTD, TanVY, et al. (2013) Essential Staphylococcus aureus toxin export system. Nat Med 19: 364–367.
37. BaeT, SchneewindO (2006) Allelic replacement in Staphylococcus aureus with inducible counter-selection. Plasmid 55: 58–63.
38. PeschelA, OttenwalderB, GotzF (1996) Inducible production and cellular location of the epidermin biosynthetic enzyme EpiB using an improved staphylococcal expression system. FEMS Microbiol Lett 137: 279–284.
39. VoyichJM, OttoM, MathemaB, BraughtonKR, WhitneyAR, et al. (2006) Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? J Infect Dis 194: 1761–1770.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2014 Číslo 8
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Disruption of Fas-Fas Ligand Signaling, Apoptosis, and Innate Immunity by Bacterial Pathogens
- Ly6C Monocyte Recruitment Is Responsible for Th2 Associated Host-Protective Macrophage Accumulation in Liver Inflammation due to Schistosomiasis
- Host Responses to Group A Streptococcus: Cell Death and Inflammation
- Pathogenicity and Epithelial Immunity