Mechanism of quinolone resistance in anaerobic bacteria.
Several recently developed quinolones have excellent activity against a broad range of aerobic and anaerobic bacteria and are thus potential drugs for the treatment of serious anaerobic and mixed infections. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. Two main mechanisms, alteration of target enzymes (gyrase and topoisomerase IV) caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. These mechanisms have also been found in anaerobic species. High-level resistance to the newer broad-spectrum quinolones often requires stepwise mutations in target genes. The increasing emergence of resistance among anaerobes may be a consequence of previous widespread use of quinolones, which may have enriched first-step mutants in the intestinal tract. Quinolone resistance in the Bacteroides fragilis group strains is strongly correlated with amino acid substitutions at positions 82 and 86 in GyrA (equivalent to positions 83 and 87 of Escherichia coli). Several studies have indicated that B. fragilis group strains possess efflux pump systems that actively expel quinolones, leading to resistance. DNA gyrase seems also to be the primary target for quinolones in Clostridium difficile, since amino acid substitutions in GyrA and GyrB have been detected in resistant strains. To what extent other mechanisms, such as mutational events in other target genes or alterations in outer-membrane proteins, contribute to resistance among anaerobes needs to be further investigated.
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Department of Laboratory Medicine, Division of Clinical Bacteriology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Edlund
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D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001421:Bacteria, Anaerobic / Q000187:drug effects* / Q000235:genetics; D001441:Bacteroides fragilis / Q000187:drug effects / Q000235:genetics; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000235:genetics
D042462:4-Quinolones; D000890:Anti-Infective Agents