title: 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.
mesh_terms: D001483:Base Sequence; D005075:Biological Evolution; D002262:Carboxy-Lyases / Q000235:genetics*; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004405:Dysentery, Bacillary / Q000209:etiology; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D004927:Escherichia coli Infections / Q000209:etiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D005798:Genes, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon; D010641:Phenotype; D012763:Shigella flexneri / Q000235:genetics / Q000472:pathogenicity; D013045:Species Specificity; D015534:Trans-Activators / Q000235:genetics*; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: C087479:CadC protein, E coli; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D015534:Trans-Activators; D002262:Carboxy-Lyases; C021520:lysine decarboxylase