Toxin mediates sepsis caused by methicillin-resistant Staphylococcus epidermidis

Li Qin, Fei Da, Emilie L. Fisher, Daniel C. S. Tan, Thuan H. Nguyen, Chih-Lung Fu, Vee Y. Tan, Joshua W. McCausland, Daniel E. Sturdevant, Hwang-Soo Joo, Shu Y. Queck, Gordon Y. C. Cheung, Michael Otto

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Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally “unintended” interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.
Original languageEnglish
Article numbere1006153
Pages (from-to)1-16
Number of pages16
JournalPLoS Pathogens
Issue number2
Publication statusPublished - 2 Feb 2017
Externally publishedYes

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  • METHICILLIN-resistant staphylococcus aureus
  • STAPHYLOCOCCUS epidermidis
  • METHICILLIN resistance
  • IMMUNE system
  • RISK factors
  • Anatomy
  • Animal cells
  • Bacteria
  • Bacterial diseases
  • Bacterial pathogens
  • Biology and life sciences
  • Blood
  • Blood cells
  • Body fluids
  • Cell biology
  • Cellular types
  • Diagnostic medicine
  • Gene expression
  • Gene regulation
  • Genetics
  • Hematology
  • Immune cells
  • Immunology
  • Infectious diseases
  • Medical microbiology
  • Medicine and health sciences
  • Microbial pathogens
  • Microbiology
  • Neutrophils
  • Organisms
  • Pathogens
  • Pathology and laboratory medicine
  • Physiology
  • Research Article
  • Sepsis
  • Signs and symptoms
  • Staphylococcal infection
  • Staphylococcus
  • Staphylococcus aureus
  • Staphylococcus epidermidis
  • Toxic agents
  • Toxicology
  • Toxins
  • White blood cells


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