The Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis

Cytotoxic necrotic factor (CNF) of Yersinia pseudotuberculosis (CNFY) is a 114-kDa toxin protein that is similar to CNF1, which is prevalent among pathogenic and saprophytic Escherichia coli isolates. In 2002, the CNF of Y. pseudotuberculosis YPIII strain (United States) was first described. The Rho family small GTP-binding proteins (GTPases) are inactivated by CNFY acting on eukaryotic cells of humans and mammals, which causes the formation of large multinucleated cells. An analysis of Y. pseudotuberculosis toxins isolated in Russia showed that the thermolabile toxin TLT described earlier was identified as identical to CNFY except for three amino acid substitutions. The TLT’s cytotoxic activity is similar to that of CNFY. Screening of Y. pseudotuberculosis strains collection isolated during the outbreaks of Far East scarletlike fever (FESLF) and in sporadic cases from patients with pseudotuberculosis/FESLF, rodents, and the environment in the Far East, Siberia, and the northwest of the Russian Federation showed that most isolates carry the specific cnfY gene allele encoding the inactive CNFY isoform. This allele contains a stop codon and two large deletions that block the production of the full-sized toxin. Interestingly, all isolates obtained from patients with FESLF, which is a severe form of pseudotuberculosis and endemic to the Far East region, contain inactivated CNFY. Possible causes of CNFY inactivation in strains associated with Far East scarletlike fever are discussed.