Involvement of topoisomerase IV and DNA gyrase
as ciprofloxacin targets in Streptococcus pneumoniae.
gonorrhoeae, CTX = ceftriaxone, gyrA ser91Phe = gyrase
A mutation, PEN = penicillin; *WHO-K calibrator strain.
Namely, PMB and C1P belong to different classes and have different mode of action: CIP inhibits DNA replication targeting DNA gyrase
(Zhao et al.
Since dozens if not hundreds of gyrase
and topoisomerase enzymes work along a bacterium's DNA at once, a large-scale invasion of quinolone molecules can swiftly reduce a whole chromosome to rubble.
Mechanism of resistance to quinolones: Target alterations, decreased accumulation and DNA gyrase
Three housekeeping genes (16S rRNA, RNA polymerase a-chain (rpoA), and DNA gyrase
B subunit (gyrB)) were sequenced, and phylogenetic trees based on rpoA and gyrB sequences were constructed.
Salmonella resistances to quinolones or fluoroquinolones are frequently observed with nalidixic acid-resistant strains accomplished by interference with bacterial DNA metabolism mediated by mutations in bacterial DNA gyrase
, and ciprofloxacin attributed to active efflux mechanisms .
The compound under research, diospyrin, binds to a novel site on a well-known enzyme, called DNA gyrase
, and inactivates the enzyme.
This antibiotic is reported to target gyrase
, topoisomerase IV and primase, and is currently in late stage pre-clinical development.
Before the emergence of bacterial plasmid-mediated quinolone resistance (PMQR) genes, research on the resistance mechanisms of (fluoro)quinolones were confined to mutations of chromosomal genes coding DNA gyrase
or topoisomerase IV in the quinolone resistance determining region (QRDR) (Hopkins et al.
Sample extracts were transported on dry ice from the field site to the Armed Forces Research Institute of Medical Sciences laboratory for confirmation testing using a well established Leptospira gyrase
subunit B conventional PCR assay.
Pharmacokinetics of the gyrase
inhibitor marbofloxacin: influence of pregnancy and lactation in sows.