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SOS response promotes horizontal dissemination of antibiotic resistance genes


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.

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We thank B. Davis, S. Chiang, A. Kane and M. Shonn for critical reading of the manuscript. We thank the New England Medical Center GRASP Center for the preparation of media and SetR-H6. This work was supported in part by funds from an NIH training grant (to J.W.B.), the DFG (to B.H.), the NIH, the Howard Hughes Medical Institute (to M.K.W.) and a pilot project grant from the NEMC GRASP Center.

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Correspondence to Matthew K. Waldor.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1: Alignment of SetR with the lambdoid repressor CI434. (PDF 45 kb)

Supplementary Figure 2: Mobility shift of the region between s086 and setR by SetR-H6. (PDF 49 kb)

Supplementary Figure Legends. (DOC 20 kb)

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Further reading

Figure 1: SOS-inducing agents activate SXT transfer.
Figure 2: SetR represses expression from PL.
Figure 3: Model of the regulatory pathway by which the SOS response augments SXT transfer.


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