Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host

• Published in: PLoS genetics 2017-05, Vol.13 (5), p.e1006816-e1006816
• Main Authors: Echeverz, Maite, García, Begoña, Sabalza, Amaia, Valle, Jaione, Gabaldón, Toni, Solano, Cristina, Lasa, Iñigo
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - genetics; Acetylglucosamine - metabolism; Adaptation, Physiological; Animals; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bile; Bile salts; Biofilms; Bioinformatics; Biology and Life Sciences; Cellulose; Chlorine; Citrobacter; Divergence; E coli; Escherichia coli; Evolution; Gallbladder; Genetic aspects; Genomes; Glucosamine; Light irradiation; Macrophages; Macrophages - microbiology; Matrices (mathematics); Medicine and Health Sciences; Mice; Microbial polysaccharides; N-Acetylglucosamine; Organs; Oxidative stress; Phage; Phages; Physical Sciences; Polysaccharides, Bacterial - deficiency; Polysaccharides, Bacterial - genetics; Polysaccharides, Bacterial - metabolism; Salmonella; Salmonella enterica - genetics; Salmonella enterica - metabolism; Salmonella enterica - pathogenicity; Salts; Survival; Ultraviolet radiation; Virulence - genetics
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006816

Many bacteria build biofilm matrices using a conserved exopolysaccharide named PGA or PNAG (poly-β-1,6-N-acetyl-D-glucosamine). Interestingly, while E. coli and other members of the family Enterobacteriaceae encode the pgaABCD operon responsible for PGA synthesis, Salmonella lacks it. The evolutionary force driving this difference remains to be determined. Here, we report that Salmonella lost the pgaABCD operon after the divergence of Salmonella and Citrobacter clades, and previous to the diversification of the currently sequenced Salmonella strains. Reconstitution of the PGA machinery endows Salmonella with the capacity to produce PGA in a cyclic dimeric GMP (c-di-GMP) dependent manner. Outside the host, the PGA polysaccharide does not seem to provide any significant benefit to Salmonella: resistance against chlorine treatment, ultraviolet light irradiation, heavy metal stress and phage infection remained the same as in a strain producing cellulose, the main biofilm exopolysaccharide naturally produced by Salmonella. In contrast, PGA production proved to be deleterious to Salmonella survival inside the host, since it increased susceptibility to bile salts and oxidative stress, and hindered the capacity of S. Enteritidis to survive inside macrophages and to colonize extraintestinal organs, including the gallbladder. Altogether, our observations indicate that PGA is an antivirulence factor whose loss may have been a necessary event during Salmonella speciation to permit survival inside the host.