title: Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response.
abstract: Toxin synthesis by Shiga toxin-producing Escherichia coli (STEC) appears to be coregulated through induction of the integrated bacteriophage that encodes the toxin gene. Phage production is linked to induction of the bacterial SOS response, a ubiquitous response to DNA damage. SOS-inducing antimicrobial agents, particularly the quinolones, trimethoprim, and furazolidone, were shown to induce toxin gene expression in studies of their effects on a reporter STEC strain carrying a chromosome-based stx2::lacZ transcriptional fusion. At antimicrobial levels above those required to inhibit bacterial replication, these agents are potent inducers (up to 140-fold) of the transcription of type 2 Shiga toxin genes (stx2); therefore, they should be avoided in treating patients with potential or confirmed STEC infections. Other agents (20 studied) and incubation conditions produced significant but less striking effects on stx2 transcription; positive and negative influences were observed. SOS-mediated induction of toxin synthesis also provides a mechanism that could exacerbate STEC infections and increase dissemination of stx genes. These features and the use of SOS-inducing antibiotics in clinical practice and animal husbandry may account for the recent emergence of STEC disease.
authors.affiliation: The Medical School, University of Newcastle, Newcastle upon Tyne, United Kingdom.
authors.forename: P T
authors.initials: PT
authors.lastname: Kimmitt
authors.forename: C R
authors.initials: CR
authors.lastname: Harwood
authors.forename: M R
authors.initials: MR
authors.lastname: Barer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics; D019453:Escherichia coli O157 / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects*; D006801:Humans; D007763:Lac Operon / Q000187:drug effects / Q000235:genetics*; D022621:Shiga Toxin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D022621:Shiga Toxin