Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus

• Published in: PLoS pathogens Vol. 6; no. 7; p. e1000982
• Main Authors: Irazoqui, Javier E, Troemel, Emily R, Feinbaum, Rhonda L, Luhachack, Lyly G, Cezairliyan, Brent O, Ausubel, Frederick M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2010; Public Library of Science (PLoS)
• Subjects: Animals; Bacteriology; Caenorhabditis elegans; Caenorhabditis elegans - microbiology; Care and treatment; Gene expression; Genetic aspects; Genetics; Genetics and Genomics/Genetics of the Immune System; Humans; Immune response; Immunology/Cellular Microbiology and Pathogenesis; Immunology/Innate Immunity; Infectious Diseases/Bacterial Infections; Intestinal Mucosa - metabolism; Intestines - microbiology; Medical research; Microbiology/Innate Immunity; Nematoda; Nematodes; Physiological aspects; Proteins; Pseudomonas aeruginosa; Pseudomonas aeruginosa - pathogenicity; Pseudomonas aeruginosa infections; Pseudomonas Infections - microbiology; Pseudomonas Infections - pathology; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - pathogenicity; Virulence - genetics; Virulence Factors - metabolism; United States; Staphylococcal Infections; Caenorhabditis elegans; Intestinal Mucosa; Intestines; Animals; Humans; Virulence; Pseudomonas aeruginosa; Pseudomonas Infections; Virulence Factors; Staphylococcus aureus
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000982

The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR) protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs). Because our data suggest that neither the P. aeruginosa nor the S. aureus-triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C. elegans, with potentially conserved roles also in mammals.