Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection

Autor: Michael Otto, Gordon Y. C. Cheung, Trung V. Ho, Dorothee Kretschmer, Hwang-Soo Joo, Yan Chen, Anthony J. Yeh, Barry N. Kreiswirth, Anthony C. Duong, Andreas Peschel
Rok vydání: 2014
Předmět:
Bacterial Diseases
Neutrophils
Staphylococcus
Bacteremia
Pathogenesis
Pathology and Laboratory Medicine
medicine.disease_cause
Medicine and Health Sciences
lcsh:QH301-705.5
Pathogen
Chromatography
High Pressure Liquid
Medical microbiology
Staphylococcal Infections
Chemotaxis
Leukocyte
Infectious Diseases
Neutrophil Infiltration
Staphylococcus aureus
Host-Pathogen Interactions
Research Article
lcsh:Immunologic diseases. Allergy
Methicillin-Resistant Staphylococcus aureus
Bacterial Toxins
Blotting
Western
Immunology
Virulence
Biology
Staphylococcal infections
Microbiology
Sepsis
Immune system
Immunity
Virology
Genetics
medicine
Animals
Humans
Molecular Biology
Immune Evasion
Biology and life sciences
medicine.disease
Methicillin-resistant Staphylococcus aureus
Immunity
Innate
Microbial pathogens
Disease Models
Animal
lcsh:Biology (General)
Bacterial pathogens
Parasitology
lcsh:RC581-607
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 10, Iss 8, p e1004298 (2014)
ISSN: 1553-7374
DOI: 10.1371/journal.ppat.1004298
Popis: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen success during infection have not yet been described. Here we show that the clonal complex (CC) 30 lineage, a major cause of hospital-associated sepsis and hematogenous complications, expresses an allelic variant of the PSMα3 peptide. We found that this variant, PSMα3N22Y, is characteristic of CC30 strains and has significantly reduced cytolytic and pro-inflammatory potential. Notably, CC30 strains showed reduced cytolytic and chemotactic potential toward human neutrophils, and increased hematogenous seeding in a bacteremia model, compared to strains in which the genome was altered to express non-CC30 PSMα3. Our findings describe a molecular mechanism contributing to attenuated pro-inflammatory potential in a main MRSA lineage. They suggest that reduced pathogen recognition via PSMs allows the bacteria to evade elimination by innate host defenses during bloodstream infections. Furthermore, they underscore the role of point mutations in key S. aureus toxin genes in that adaptation and the pivotal importance PSMs have in defining key S. aureus immune evasion and virulence mechanisms.
Author Summary 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.
Databáze: OpenAIRE
Externí odkaz: