Inhibition of Repressor Gene Spreads Antibiotic Resistance

Researchers have identified a mechanism by which therapeutic agents can promote the spread of antibiotic resistance genes between different species of bacteria.

Investigators at Tufts University School of Medicine (Boston, MA, USA) focused their study on the collection of antibiotic-resistance genes called SXT that have been responsible for conferring resistance on four antibiotics (chloramphenicol, sulphamethoxazole, trimethoprim, and streptomycin) to nearly all strains of Vibrio cholerae in Asia.

They reported in the December 21, 2003, online edition of Nature that setR, one of the SXT genes that encode the SetR repressor protein, might be the key to the spread of antibiotic resistance. Normally SetR represses the setC and setD genes, which are activators of the excision and transfer of SXT. However, when the bacteria are placed under metabolic stress, their "SOS response” inhibits the activity of SetR, which increases the expression of genes necessary for SXT transfer and hence the frequency of transfer. One of the factors that can trigger the "SOS response” is treatment with antibiotics, including the frequently prescribed ciprofloxacin.

"This new understanding of the mechanism of transfer is very worrisome, for it shows how indiscriminant antibiotic use can promote the dissemination of antibiotic resistance,” explained senior author Dr. Matthew K. Waldor, associate professor of molecular biology and microbiology at Tufts University School of Medicine. "This is very different from the process by which antibiotic use selects for resistant organisms that are already in the population. We have shown how antibiotic use can promote the evolution of new antibiotic-resistant organisms that have obtained their resistance genes from other species.”



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