SOS response promotes horizontal dissemination of antibiotic resistance genes

John W. Beaber, Bianca Hochhut and Matthew K. Waldor ()
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John W. Beaber: Tufts University School of Medicine and Howard Hughes Medical Institute
Bianca Hochhut: Tufts University School of Medicine and Howard Hughes Medical Institute
Matthew K. Waldor: Tufts University School of Medicine and Howard Hughes Medical Institute

Nature, 2004, vol. 427, issue 6969, 72-74

Abstract: Abstract Mobile genetic elements have a crucial role in spreading antibiotic resistance genes among bacterial populations. Environmental and genetic factors that regulate conjugative transfer of antibiotic resistance genes in bacterial populations are largely unknown1. Integrating conjugative elements (ICEs) are a diverse group of mobile elements that are transferred by means of cell–cell contact and integrate into the chromosome of the new host2. SXT is a ∼100-kilobase ICE derived from Vibrio cholerae that encodes genes that confer resistance to chloramphenicol, sulphamethoxazole, trimethoprim and streptomycin3. SXT-related elements were not detected in V. cholerae before 1993 but are now present in almost all clinical V. cholerae isolates from Asia4. ICEs related to SXT are also present in several other bacterial species and encode a variety of antibiotic and heavy metal resistance genes4,5,6,7. Here we show that SetR, an SXT encoded repressor, represses the expression of activators of SXT transfer. The ‘SOS response’ to DNA damage alleviates this repression, increasing the expression of genes necessary for SXT transfer and hence the frequency of transfer. SOS is induced by a variety of environmental factors and antibiotics, for example ciprofloxacin, and we show that ciprofloxacin induces SXT transfer as well. Thus, we present a mechanism by which therapeutic agents can promote the spread of antibiotic resistance genes.

Date: 2004
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DOI: 10.1038/nature02241

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