title: Salmonella promotes virulence by repressing cellulose production.
abstract: Cellulose is the most abundant organic polymer on Earth. In bacteria, cellulose confers protection against environmental insults and is a constituent of biofilms typically formed on abiotic surfaces. We report that, surprisingly, Salmonella enterica serovar Typhimurium makes cellulose when inside macrophages. We determine that preventing cellulose synthesis increases virulence, whereas stimulation of cellulose synthesis inside macrophages decreases virulence. An attenuated mutant lacking the mgtC gene exhibited increased cellulose levels due to increased expression of the cellulose synthase gene bcsA and of cyclic diguanylate, the allosteric activator of the BcsA protein. Inactivation of bcsA restored wild-type virulence to the Salmonella mgtC mutant, but not to other attenuated mutants displaying a wild-type phenotype regarding cellulose. Our findings indicate that a virulence determinant can promote pathogenicity by repressing a pathogen's antivirulence trait. Moreover, they suggest that controlling antivirulence traits increases long-term pathogen fitness by mediating a trade-off between acute virulence and transmission.
authors.affiliation: Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; Yale Microbial Sciences Institute, West Haven, CT 06516; and.
authors.forename: Mauricio H
authors.initials: MH
authors.lastname: Pontes
authors.affiliation: Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; Yale Microbial Sciences Institute, West Haven, CT 06516; and Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536;
authors.forename: Jeongjoon
authors.initials: J
authors.lastname: Choi
authors.affiliation: Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; Yale Microbial Sciences Institute, West Haven, CT 06516; and eduardo.groisman@yale.edu.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002482:Cellulose / Q000096:biosynthesis*; D005964:Glucosyltransferases / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000235:genetics; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; D002482:Cellulose; D005964:Glucosyltransferases; C478648:cellulose synthase; D008274:Magnesium
keywords: ATP; biofilm; magnesium
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