Amino acid variation in the GyrA subunit of bacteria potentially associated with natural resistance to fluoroquinolone antibiotics.
In studies of genetic diversity in natural microbial populations, we have analyzed nucleotide sequences in the quinolone resistance-determining region of the bacterial gyrA gene in ciprofloxacin-resistant and nonselected soil bacteria obtained from the environment. It is apparent that this sequence is highly variable, and resistance to fluoroquinolone antibiotics occurring in environmental populations of bacteria is due at least in part to natural sequence variation in this domain. We suggest that the development of new antimicrobial agents, including completely synthetic antimicrobials such as the fluoroquinolones, should incorporate the analysis of resistance mechanisms among microbes in natural environments; these studies could predict potential mechanisms of resistance to be encountered in subsequent clinical use of the agents and would guide chemical modification designed to evade resistance development.
Waters
B
B
TerraGen Diversity Inc., Vancouver, British Columbia, Canada.
Davies
J
J
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics*; D024841:Fluoroquinolones; D014644:Genetic Variation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D046911:Macromolecular Substances; D004250:DNA Topoisomerases, Type II