Association of adhesive, invasive, and virulent phenotypes of Salmonella typhimurium with autonomous 60-megadalton plasmids.

The plasmid DNA content of six invasive and adhesive strains of Salmonella typhimurium was determined, and all six strains (CR8500 [S850], CR6600 [TML], W118, NY, PR, and S2204) were found to harbor at least one plasmid equivalent in size to the 60-megadalton plasmid ("cryptic" plasmid), pSLT, which is normally resident in S. typhimurium strain LT2. The role of such 60-megadalton plasmids in the adhesive and invasive properties of strain CR6600, a commonly encountered salmonella pathogen that produces type 1 fimbriae, and strain CR8500, a representative FIRN biotype which does not produce type 1 fimbriae, was studied further by obtaining derivatives of these strains that no longer harbored an autonomous 60-megadalton plasmid. Strains CR6260 and CR6190 and strains CR8100 and CR8353, which were "cured" derivatives of strains CR6600 and CR8500, respectively, were significantly less adhesive and invasive in the HeLa cell test. A 53.5-megadalton colicin plasmid harbored by strain CR6600 did not detectably influence these properties. Additionally, strain CR6260 was avirulent, and strain CR8100 was 1,000 to 10,000-fold less virulent for orally infected mice as compared with their respective parental strains. Significantly, the virulence of strain CR8100 correlated with tissue colonization by bacteria that exhibited autonomous copies of a 60-megadalton plasmid. We propose that this plasmid exists in both autonomous and integrated states and that the in vivo environment selects for bacteria with autonomous plasmid copies which can express the virulent phenotype, thus enabling such strains to survive the defense mechanisms of the host.