Abstract
The spread of methicillin-resistant Staphylococcus aureus (MRSA) in the community, hospitals and in livestock is mediated by highly diverse virulence factors that include secreted toxins, superantigens, enzymes and surface-associated adhesins allowing host adaptation and colonization. Here, we combined proteogenomics, secretome and phenotype analyses to compare the secreted virulence factors in selected S. aureus isolates of the dominant human- and livestock-associated genetic lineages CC8, CC22, and CC398. The proteogenomic comparison revealed 2181 core genes and 1306 accessory genes in 18 S. aureus isolates reflecting the high genome diversity. Using secretome analysis, we identified 869 secreted proteins with 538 commons in eight isolates of CC8, CC22, and CC398. These include 64 predicted extracellular and 37 cell surface proteins that account for 82.4% of total secretome abundance. Among the top 10 most abundantly secreted virulence factors are the major autolysins (Atl, IsaA, Sle1, SAUPAN006375000), lipases and lipoteichoic acid hydrolases (Lip, Geh, LtaS), cytolytic toxins (Hla, Hlb, PSMβ1) and proteases (SspB). The CC398 isolates showed lower secretion of cell wall proteins, but higher secretion of α- and β-hemolysins (Hla, Hlb) which correlated with an increased Agr activity and strong hemolysis. CC398 strains were further characterized by lower biofilm formation and staphyloxanthin levels because of decreased SigB activity. Overall, comparative secretome analyses revealed CC8- or CC22-specific enterotoxin and Spl protease secretion as well as Agr- and SigB-controlled differences in exotoxin and surface protein secretion between human-specific and zoonotic lineages of S. aureus.
Highlights
Author’s Choice los Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398*□S
The proteogenome comparisons of the 18 S. aureus isolates are shown in a presence/absence Table indicating the frequency of all proteins in 18 S. aureus isolates
We extracted the virulence factors, including cytolytic toxins, superantigens and enterotoxins, toxin-antitoxin systems, immune evasion cluster proteins, surface-associated proteins with MSCRAMM and secretable expanded repertoire adhesive molecules” (SERAMs) functions, and other proteins annotated as virulence factors to highlight the diversity of the pathogenicity related factors in the 18 isolates
Summary
Author’s Choice los Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398*□S. The spread of methicillin-resistant Staphylococcus aureus (MRSA) in the community, hospitals and in livestock is mediated by highly diverse virulence factors that include secreted toxins, superantigens, enzymes and surface-associated adhesins allowing host adaptation and colonization. We combined proteogenomics, secretome and phenotype analyses to compare the secreted virulence factors in selected S. aureus isolates of the dominant human- and livestock-associated genetic lineages CC8, CC22, and CC398. Comparative secretome analyses revealed CC8- or CC22-specific enterotoxin and Spl protease secretion as well as Agr- and SigB-controlled differences in exotoxin and surface protein secretion between human-specific and zoonotic lineages of S. aureus. Human MRSA strains include hospital-acquired (HA) and community-acquired (CA) MRSA isolates with increased virulence, with respect to severe soft tissue infections, such as strain USA300 [7]. From the ‡Institute for Biology-Microbiology, Freie Universitat Berlin, D-14195 Berlin, Germany; §Center for Biotechnology, Bielefeld University, D-33594 Bielefeld, Germany; ¶Robert Koch Institute, Advanced Light and Electron Microscopy, D-13353 Berlin, Germany; ʈInstitute of Microbiology and Epizootics, Centre for Infection Medicine, Freie Universitat Berlin, D-14153 Berlin, Germany; **Robert Koch Institute, Wernigerode Branch, D-38855 Wernigerode, Germany; ‡‡Institute of Hygiene, University Hospital Munster, D-48149 Munster, Germany; §§Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK; ¶¶Department Isotope Biogeochemistry, Helmholtz Centre for Environmental Research-UFZ, D-04318 Leipzig, Germany; ʈʈChair of Geobiotechnology, Technische Universitat Berlin, D-13355 Berlin, Germany; ‡‡‡Institute for Microbiology, University of Greifswald, D-17489 Greifswald, Germany
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
