Staphylococcal Biofilm Exopolysaccharide Protects against Caenorhabditis elegans Immune Defenses

PLoS Pathogens

Jessica M Gaiani¹  Costi D Sifri²  Jakob Begun³  Holger Rohde⁴  Frederick M Ausubel⁵  Dietrich Mack⁶  Stephen B Calderwood⁷ 

[1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America;Division of Infectious Diseases and International Health, University of Virginia Health System, Charlottesville, Virginia, United States of America;Division of Infectious Diseases, Massachusetts General Hospital, Boston Massachusetts, United States of America;Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany;Medical Microbiology and Infectious Diseases, The School of Medicine, University of Wales Swansea, Swansea, United Kingdom

关键词: Staphylococcus epidermidis;    Caenorhabditis elegans;    Nematode infections;    Gastrointestinal tract;    Bacterial biofilms;    Staphylococcus aureus;    Bacterial pathogens;    Exopolysaccharides;   

DOI  :  10.1371/journal.ppat.0030057

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host–pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation.

【 授权许可】

CC BY