Salmonella promotes virulence by repressing cellulose production

Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5183-8. doi: 10.1073/pnas.1500989112. Epub 2015 Apr 6.

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.

Keywords: ATP; biofilm; magnesium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Bacterial Proteins / metabolism
  • Cellulose / biosynthesis*
  • Glucosyltransferases / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Magnesium / pharmacology
  • Mice
  • Mutation / genetics
  • Phagocytes / drug effects
  • Phagocytes / metabolism
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / pathogenicity*
  • Virulence

Substances

  • Bacterial Proteins
  • Adenosine Triphosphate
  • Cellulose
  • Glucosyltransferases
  • cellulose synthase
  • Magnesium