title: Exposure of Salmonella enterica Serovar typhimurium to a protective monoclonal IgA triggers exopolysaccharide production via a diguanylate cyclase-dependent pathway.
abstract: Sal4 is a monoclonal polymeric IgA antibody directed against the O antigen (O-Ag) of Salmonella enterica serovar Typhimurium (S. Typhimurium), which is sufficient to protect mice against intestinal infections from S. Typhimurium. We recently reported that the exposure of S. Typhimurium to Sal4 results in the immediate loss of flagellum-based motility, in alterations to the outer membrane (OM) integrity, and in the concomitant appearance of a mucoid phenotype that is reminiscent of cells in the earliest stages of biofilm formation. We demonstrate here that prolonged (>4 h) exposure of S. Typhimurium to Sal4 at 37 °C (but not at ambient temperature [25°C]) results in measurable exopolysaccharide (EPS) accumulation and biofilm formation on both borosilicate glass surfaces and polystyrene microtiter plates. The polysaccharide produced by S. Typhimurium in response to Sal4 contains cellulose, in addition to O-Ag capsule and colanic acid. EPS production was dependent on YeaJ, a proposed inner membrane-localized diguanylate cyclase (DGC) and a known regulator of cellulose biosynthesis. An S. Typhimurium ΔyeaJ strain was unable to produce cellulose or form a biofilm in response to Sal4. Conversely, the overexpression of yeaJ in S. Typhimurium enhanced Sal4-induced biofilm formation and resulted in increased intracellular levels of cyclic dimeric guanosine monophosphate (c-di-GMP) compared to that of a wild-type control; this strongly suggests that YeaJ is indeed a functional DGC. Based on these data, we speculate that Sal4, by virtue of its ability to associate with the O-Ag and to induce OM stress, renders S. Typhimurium avirulent by triggering a c-di-GMP-dependent signaling pathway via YeaJ that leads to the suppression of bacterial motility while simultaneously stimulating EPS production.
authors.affiliation: Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Jayaleka J
authors.initials: JJ
authors.lastname: Amarasinghe
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: D'Hondt
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Waters
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Mantis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D009154:Mutation; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D011135:Polysaccharides, Bacterial; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase