Quorum‐sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization

• Published in: EMBO reports Vol. 19; no. 5
• Main Authors: Haller, Samantha, Franchet, Adrien, Hakkim, Abdul, Chen, Jing, Drenkard, Eliana, Yu, Shen, Schirmeier, Stefanie, Li, Zi, Martins, Nelson, Ausubel, Frederick M, Liégeois, Samuel, Ferrandon, Dominique
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Blackwell Publishing Ltd; EMBO Press; John Wiley and Sons Inc
• Subjects: Animals; Bacteremia; Bacteria; Bacterial Proteins - genetics; Caenorhabditis elegans - microbiology; competition opsonization‐detection by pattern recognition receptors; DEAD-box RNA Helicases - genetics; Detection; Drosophila; Drosophila melanogaster - immunology; Drosophila melanogaster - microbiology; Drosophila Proteins - genetics; Drosophila Proteins - immunology; EMBO19; EMBO23; Gene Expression Regulation, Bacterial; Hemocoel; Hemocytes; Immune response; Immune response (cell-mediated); Immune system; infection route; Infections; Insects; intestinal infection; Intestine; Intestines - immunology; Intestines - microbiology; Life Sciences; Ligases - genetics; Mutants; Opsonization; Phagocytosis; Proteins; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - pathogenicity; quorum sensing; Quorum Sensing - genetics; Receptors, Pattern Recognition - immunology; RhlR protein; Transcription Factors - genetics; Virulence; phagocytosis; infection route; quorum sensing; intestinal infection; competition opsonization‐detection by pattern recognition receptors
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201744880

When Drosophila melanogaster feeds on Pseudomonas aeruginosa , some bacteria cross the intestinal barrier and eventually proliferate in the hemocoel. This process is limited by hemocytes through phagocytosis. P. aeruginosa requires the quorum‐sensing regulator RhlR to elude the cellular immune response of the fly. RhlI synthesizes the autoinducer signal that activates RhlR. Here, we show that rhlI mutants are unexpectedly more virulent than rhlR mutants, both in fly and in nematode intestinal infection models, suggesting that RhlR has RhlI‐independent functions. We also report that RhlR protects P. aeruginosa from opsonization mediated by the Drosophila thioester‐containing protein 4 (Tep4). RhlR mutant bacteria show higher levels of Tep4‐ mediated opsonization, as compared to rhlI mutants, which prevents lethal bacteremia in the Drosophila hemocoel. In contrast, in a septic model of infection, in which bacteria are introduced directly into the hemocoel, Tep4 mutant flies are more resistant to wild‐type P. aeruginosa, but not to the rhlR mutant. Thus, depending on the infection route, the Tep4 opsonin can either be protective or detrimental to host defense. Synopsis Tep4‐mediated opsonization blocks rhlR but not rhlI quorum‐sensing mutants during intestinal Pseudomonas infection in flies. In contrast, Tep4 is detrimental to host defense upon septic injury, highlighting the importance of the infection route. P. aeruginosa rhlI ‐null mutants display an intermediate virulence between wild‐type and rhlR ‐null mutants. RhlR but not RhlI allows bacteria to proliferate in the hemocoel by escaping early phagocytosis. Tep4 mediates specific and efficient opsonization of rhlR but not wild‐type P. aeruginosa . Tep4 mutants are sensitive to intestinal infection by ingested P. aeruginosa , but not to injected bacteria. Graphical Abstract Tep4‐mediated opsonization blocks rhlR but not rhlI quorum‐sensing mutants during intestinal Pseudomonas infection in flies. In contrast, Tep4 is detrimental to host defense upon septic injury, highlighting the importance of the infection route.