Researchers have discovered that a common mutation in Salmonella, which makes it resistant to fluoroquinolones, an important class of antibiotics, also allows survival of bacteria in the presence of other antibiotics or the biocide, triclosan. Triclosan is an antibacterial and antifungal agent found in toothpastes, deodorants and soaps.
In a new paper, they have demonstrated that a mutation which changes DNA gyrase – the target of fluoroquinolones – in Salmonella alters the structure of bacterial DNA by changing the tightness of chromosome coiling. These changes induce stress responses, which protect the bacterium and allow survival in the presence of numerous unrelated antibiotics including triclosan.
The study explored the effects of substituting two specific amino acids within DNA gyrase to recreate common changes seen in resistant strains isolated from patients. Although both mutants were resistant to quinolone antibiotics, one substitution also resulted in a significant increase in survival when exposed to 25 other drugs. These data indicate that the nature of the mutation is important in surviving exposure to antibiotics.
The research also showed that the change in gyrase altered susceptibility to the range of antibiotics by changing supercoiling of the chromosome rather than influencing how much drug was accumulated within the bacterium or other changes to cellular metabolism including the generation of reactive oxygen species.
The study demonstrates that a common mechanism of resistance to one group of antibiotics provides protection against other types of antibiotic. This suggests that such bacteria will survive better in the presence of many antimicrobials including biocides, and gives scientists more vital information in the fight against antibiotic resistance and the development of new drugs.
Differences in growth between strains and the impact of the addition of half the MIC for SL1344 of ampicillin, gentamicin, and triclosan on growth. The graph shows average culture OD values at 4 and 8 h postinoculation; averages that are statistically significantly different from those of the parent strain, SL1344, are marked by asterisks. Open bars indicate SL1344, blue bars indicate L821 (GyrA Ser83Phe), and red bars indicate L825 (GyrA Asp87Gly). Credit and link: doi:10.1128/mBio.00273-13
Senior author Laura Piddock of the University of Birmingham said, "This study shows that use of a common antibiotic confers fundamental changes allowing bacteria to survive exposure to several antibiotics plus an antimicrobial found in products commonly used in the home."
Lead author Mark Webber, also from University of Birmingham, added, "Our work has helped understand how developing antibiotic resistance can change the biology of bacteria in a profound way. Identifying the conditions which select for resistant bacteria and promote their survival will help use current drugs in better ways."
Funded by the Biotechnology and Biological Sciences Research Council and the Medical Research Council.
Citation: Mark A. Webber, Vito Ricci, Rebekah Whitehead, Meha Patel, Maria Fookes, Alasdair Ivens and Laura J. V. Piddock, 'Clinically Relevant Mutant DNA Gyrase Alters Supercoiling, Changes the Transcriptome, and Confers Multidrug Resistance', 23 July 2013 mBio vol. 4 no. 4 doi:10.1128/mBio.00273-13