The role of cfa gene in ampicillin tolerance in Shigella

BACKGROUND: Bacterial dysentery is an intestinal infectious disease caused by Shigella. The resistance of Shigella species to ampicillin has increased rapidly. Besides resistance, bacteria in a state of tolerance to antibiotics can also lead to the failure of infectious diseases therapy. PURPOSE: The genetic mechanism of antibiotic tolerance remains largely unexplored. The current study aimed to investigate the mechanisms of antibiotic tolerance and to provide novel strategies for the prevention of drug resistance of Shigella. METHODS: We exposed Shigella to lethal doses of ampicillin to obtain tolerant strain. The tolerant strain was sequenced to screen non-single-nucleotide polymorphisms and Indels. We also quantitated the relative expression of gene by RT-PCR. RESULTS: There was one nonsynonymous mutation in the 2252304 loci of the cfa gene (G to A/Val to Met) and 10 Indels in the noncoding regions of different genes. The expression of the cfa gene was 7.56-fold higher in the tolerant strain than in the wild-type strain. CONCLUSION: Our results showed that Shigella could be tolerated to ampicillin, and the cfa gene might be associated with antibiotic tolerance by increasing its expression. Our data suggest that cfa gene might be a target for overcoming drug tolerance, delaying the occurrence of drug resistance to some extent.