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 unknown. 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 host. SXT is a approximately 100-kilobase ICE derived from Vibrio cholerae that encodes genes that confer resistance to chloramphenicol, sulphamethoxazole, trimethoprim and streptomycin. SXT-related elements were not detected in V. cholerae before 1993 but are now present in almost all clinical V. cholerae isolates from Asia. ICEs related to SXT are also present in several other bacterial species and encode a variety of antibiotic and heavy metal resistance genes. 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.     

Comparison of SXT and R391, two conjugative integrating elements: definition of a genetic backbone for the mobilization of resistance determinants

The SXT element (SXT) is becoming an increasingly prevalent vector for the dissemination of antibiotic resistances in Vibrio cholerae. SXT is a member of a larger family of elements, formerly defined as IncJ plasmids, that are self-transmissible by conjugation and integrate site-specifically into the host chromosome. Comparison of the DNA sequences of SXT and R391, an IncJ element from Providencia rettgeri, indicate that these elements consist of a conserved backbone that mediates the regulation, excision/integration and conjugative transfer of the elements. Both elements have insertions into this backbone that either confer the element-specific properties or are of unknown function. Interestingly, the conserved SXT and R391 backbone apparently contains hotspots for insertion of additional DNA sequences. This backbone represents a scaffold for the mobilization of genetic material between a wide range of Gram-negative bacteria, allowing for rapid adaptation to changing envi ronments. RID="*" ID="*"Corresponding author.