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 c ause persistent asymptomatic infections in pigs, exists in two phenotypes. One phenotype, which is called adhesive, was shown to produce pill, is adhe sive to porcine enterocytes, is readily phagocytized, and then survives int racellularly in phagocytes. The other phenotype, termed non-adhesive, does not produce pill, does not attach to enterocytes, is phagocytized less effi ciently, and does not survive within the phagocyte. Cells in each phenotype can freely switch to the other phenotype at a fairly high frequency and th us the shift between each phenotype is phase variation. Further analysis of these phenotypes identified 4 additional characteristics that were co-regu lated by phase variation. The first is the enterocyte-specific adhesin, whi ch was shown to be type 1 fimbriae. Mutations in fimA, the major pilin mole cule, led to a decreased ability to colonize the gut of pigs and mice. The second characteristic is O-antigen production. Adhesive cells produce a lon g O-antigen (up to 18 subunits) while non-adhesive cells do not (only 1-2 s ubunits). The long O-antigen produced by the adhesive cells leads to resist ance 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 p roduction of colonies growing on Evans blue-Uranine plates. The relationshi p of this trait to in vivo survival or virulence is not known but ebu is ge netically related to a family of transcriptional activators. The fourth loc us, pry is located on the virulence plasmid and a mutation in pry results i n delayed time to death in mice. It is hypothesized that the adhesive pheno type 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.