A Large Family of Antivirulence Regulators Modulates the Effects of Transcriptional Activators in Gram-negative Pathogenic Bacteria

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We report here the identification and characterization of a new family of negative regulators in Gram-negative bacteria, including many pathotypes of diarrheagenic Enterobacteriaceae and members of the Pasteurellaceae. Members of this regulator family in enteroaggregative (EAEC) and enterotoxigenic E. coli (ETEC) and in Citrobacter rodentium downregulate the expression of positive regulator partners AggR, CfaD/Rns and RegA, respectively, all members of the AraC/XylS family of regulators. Accordingly, we propose the name ANR (AraC Negative Regulators) for this family. ANR members orf60 (termed Aar), orf02851 (Rnr), orf0450 and orf01070 (Cnr) from EAEC, C. rodentium and ETEC respectively were characterized in this study. Deletion of ANR homologs upregulated the expression of AggR and RegA in EAEC strain 042 and C. rodentium respectively; overexpression of orf60, orf02851, orf0450 and orf01070 in EAEC strain 042 down-regulated AggR. C. rodentium harboring a null mutation in orf02851 exhibited a significant increase in expression of the regA and RegA-regulated fimbriae. The orf02851 mutant showed higher levels of C. rodentium in feces and colonic contents, and greater weight loss compared to mice inoculated with the wild-type.

Vyšlo v časopise: A Large Family of Antivirulence Regulators Modulates the Effects of Transcriptional Activators in Gram-negative Pathogenic Bacteria. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004153
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004153

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