Homologues of Insecticidal Toxin Complex Genes in Yersinia enterocolitica Biotype 1A and Their Contribution to Virulence

Abstract

Yersinia enterocolitica is an enteric pathogen that consists of six biotypes: 1A, 1B, 2, 3, 4, and 5. Strains of the latter five biotypes can carry a virulence plasmid, known as pYV, and several well-characterized chromosomally encoded virulence determinants. Y. enterocolitica strains of biotype 1A lack the virulence-associated markers of pYV-bearing strains and were once considered to be avirulent. There is growing epidemiological, clinical, and experimental evidence, however, to suggest that some biotype 1A strains are virulent and can cause gastrointestinal disease. To identify potential virulence genes of pathogenic strains of Y. enterocolitica biotype 1A, we used genomic subtractive hybridization to determine genetic differences between two biotype 1A strains: an environmental isolate, Y. enterocolitica IP2222, and a clinical isolate, Y. enterocolitica T83. Among the Y. enterocolitica T83-specific genes we identified were three, tcbA, tcaC, and tccC, that showed homology to the insecticidal toxin complex (TC) genes first discovered in Photorhabdus luminescens. The Y. enterocolitica T83 TC gene homologues were expressed by Y. enterocolitica T83 and were significantly more prevalent among clinical biotype 1A strains than other Yersinia isolates. Inactivation of the TC genes in Y. enterocolitica T83 resulted in mutants which were attenuated in the ability to colonize the gastrointestinal tracts of perorally infected mice. These results indicate that products of the TC gene complex contribute to the virulence of some strains of Y. enterocolitica biotype 1A, possibly by facilitating their persistence in vivo.

Role of Yersinia pestis Toxin Complex Family Proteins in Resistance to Phagocytosis by Polymorphonuclear Leukocytes

“…This is in agreement with previous studies which have shown that Y. pestis and Yersinia pseudotuberculosis Tc proteins are not toxic to Sf9 insect cells, M. sexta larvae, or X. cheopis (12,13) but are active against mammalian NIH 3T3 and Caco-2 cells (12). Additionally, Yersinia enterocolitica Tc protein homologues are only mildly insecticidal and nematocidal when fed orally (33)(34)(35) but are important in colonization of the gastrointestinal tract of mice (36). In contrast, the Tc proteins of P. luminescens, the closely related Xenorhabdus nematophilus, and Yersinia entomophaga (isolated from a diseased Costelytra zealandica larva) are all highly insecticidal (3,34,37,38).…”

Evolutionary Dynamics of the Yersinia enterocolitica Complex

“…Clustering based on BAPS suggests BT 1A as a separate species cluster, and given the very different nature and environment of BT 1A, this is a reasonable suggestion. Although BT 1A is considered non-pathogenic, it is isolated from healthy and ill individuals (Bottone, 1999;Tennant, Grant and Robins-Browne, 2003;Tennant, Skinner, Joe and Robins-Browne, 2005). Research shows though that the ability to cause disease and the mechanism to do so differs markedly from the other pathogenic Y. enterocolitica BT, in that survival and hibernation inside macrophages might play a role (McNally, et al, 2006).…”

The Main Virulence Determinant of Yersinia entomophaga MH96 Is a Broad-Host-Range Toxin Complex Active against Insects

“…The toxin complex A (TCA)-like (tcaB) gene of Yersinia pestis CO92 contains a frameshift mutation, and the toxin complex B (TCB)-like (tcaC) gene contains an internal deletion (51), indicative of a loss of function, while the corresponding TCA-like and TCBlike orthologues in Y. pestis KIM and 91001 do not (18,62). Tennant et al (66) showed that mutations in each of the Yersinia enterocolitica biotype 1A T83 genes, TCA-like (tcbA), TCB-like (tcaC), and TCC-like (tccC) genes, resulted in a reduced ability to colonize the intestinal tracts of BALB/c mice compared to the wild-type strain. This suggests that the TC proteins may enhance the persistence of the host bacterium, a scenario postulated by Erickson et al (23), who found no Yersinia pseudotuberculosis TC-related toxicity toward the rat flea Xenopsylla cheopis even though expression of the TC genes is upregulated during the disease process.…”