CadC Is the Preferential Target of a Convergent Evolution Driving Enteroinvasive Escherichia coli toward a Lysine Decarboxylase-Defective Phenotype

Abstract

Enteroinvasive E. coli (EIEC), like Shigella, is the etiological agent of bacillary dysentery, a particularly severe syndrome in children in developing countries. All EIEC strains share with Shigella the inability to synthesize lysine decarboxylase (the LDC phenotype). The lack of this function is considered a pathoadaptive mutation whose emergence was necessary to obtain the full expression of invasiveness. Cadaverine, the product of lysine decarboxylation, is a small polyamine which interferes mainly with the inflammatory process induced by dysenteric bacteria. Genes coding for lysine decarboxylase and its transporter constitute a single operon (cadBA) and are expressed at low pH under the positive control of CadC. This regulator is an inner membrane protein that is able to sense pH variation and to respond by transcriptionally activating the cadBA genes. In this study we show that, unlike in Shigella, mutations affecting the cad locus in the EIEC strains we have analyzed are not followed by a novel gene arrangement and that the LCD ؊ phenotype is dependent mainly on inactivation of the cadC gene. Introduction of a functional CadC restores cadaverine expression in all EIEC strains harboring either an IS2 element or a defective cadC promoter. Comparative analysis between the cad regions of S. flexneri and EIEC suggests that the LDC ؊ phenotype has been attained by different strategies within the E. coli species.

Metabolic control through ornithine and uracil of epithelial cell invasion by Shigella flexneri

“…In these pathways, the genes codA, speF and cadA are present in E. coli but absent in S. flexneri. As has been suggested for cadA, the absence of these genes, which are marked with *, could be related to the pathoadaptative evolution which led from commensal E. coli to modern Shigella (Casalino et al, 2003;Maurelli et al, 1998), supporting the critical role of uracil, putrescine and cadaverine in virulence gene expression identified in this study. In addition, argF, which encodes one of the isozymes for ornithine carbamoyltransferase, is absent in S. flexneri and a transposable element IS1 alters the promoter region of the gene speB, responsible for the conversion of agmatine to putrescine.…”

Pathoadaptive Mutation That Mediates Adherence of Shiga Toxin-Producing Escherichia coli O111

“…Furthermore, it has been proposed that the main strategy adopted by Shigella and enteroinvasive E. coli strains for silencing the cad operon relies on mutations in cadC (13). Recent data indicate that Shigella and enteroinvasive E. coli strains have silenced the cad locus through several strategies, i.e., lack of the entire cad locus in S. flexneri or the presence of the cad locus with only one point mutation in the cadC promoter in one enteroinvasive E. coli strain (12).…”

Molecular Characterization of Virulence Determinants of Stenotrophomonas Maltophilia Strains Isolated from Patients Affected by Cystic Fibrosis

“…Total genomic DNA extraction, restnction digestion, electrophoresis, PCR amplification, and DNA fragment purification were carried out as described previously (12). DNA probes were obtained by PCR amplification.…”