Phase variable switching of in vivo and environmental phenotypes of Salmonella typhimurium.

Previously it was shown that S. typhimurium strain 798, which is known to cause persistent asymptomatic infections in pigs, exists in two phenotypes. One phenotype, which is called adhesive, was shown to produce pili, is adhesive to porcine enterocytes, is readily phagocytized, and then survives intracellularly in phagocytes. The other phenotype, termed non-adhesive, does not produce pili, does not attach to enterocytes, is phagocytized less efficiently, and does not survive within the phagocyte. Cells in each phenotype can freely switch to the other phenotype at a fairly high frequency and thus the shift between each phenotype is phase variation. Further analysis of these phenotypes identified 4 additional characteristics that were co-regulated by phase variation. The first is the enterocyte-specific adhesin, which was shown to be type 1 fimbriae. Mutations in fimA, the major pilin molecule, led to a decreased ability to colonize the gut of pigs and mice. The second characteristic is O-antigen production. Adhesive cells produce a long O-antigen (up to 18 subunits) while non-adhesive cells do not (only 1-2 subunits). The long O-antigen produced by the adhesive cells leads to resistance to serum and appears to be the result of phase variable expression of rfaL. A third locus, ebu, has been identified based on differential color production of colonies growing on Evans blue-Uranine plates. The relationship of this trait to in vivo survival or virulence is not known but ebu is genetically related to a family of transcriptional activators. The fourth locus, prv is located on the virulence plasmid and a mutation in prv results in delayed time to death in mice. It is hypothesized that the adhesive phenotype is the in vivo, virulent form, while the non-adhesive phenotype is the environmental, avirulent form. By modulating the fraction of cells in each phase, persistent asymptomatic infections can be promoted.