Small-Colony Mutants of Staphylococcus aureus Allow Selection of Gyrase-Mediated Resistance to Dual-Target Fluoroquinolones

@article{Pan2002SmallColonyMO,
  title={Small-Colony Mutants of Staphylococcus aureus Allow Selection of Gyrase-Mediated Resistance to Dual-Target Fluoroquinolones},
  author={X. Pan and Penelope J Hamlyn and R. Tal{\'e}ns-Visconti and F. Alovero and R. Manzo and L. Fisher},
  journal={Antimicrobial Agents and Chemotherapy},
  year={2002},
  volume={46},
  pages={2498 - 2506}
}
ABSTRACT Fluoroquinolones acting equally through DNA gyrase and topoisomerase IV in vivo are considered desirable in requiring two target mutations for emergence of resistant bacteria. To investigate this idea, we have studied the response of Staphylococcus aureus RN4220 to stepwise challenge with sparfloxacin, a known dual-target agent, and with NSFQ-105, a more potent sulfanilyl fluoroquinolone that behaves similarly. First-step mutants were obtained with both drugs but only at the MIC. These… Expand
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References

SHOWING 1-10 OF 52 REFERENCES
Quinolone Resistance Mutations in Streptococcus pneumoniae GyrA and ParC Proteins: Mechanistic Insights into Quinolone Action from Enzymatic Analysis, Intracellular Levels, and Phenotypes of Wild-Type and Mutant Proteins
  • Xiao-Su Pan, G. Yague, L. Fisher
  • Medicine, Biology
  • Antimicrobial Agents and Chemotherapy
  • 2001
TLDR
Pneumoniae gyrase gyrA and topoisomerase IV parC genes encoding respective Ser81Phe and Ser79Phe mutations provide strong support for a model in which quinolones kill S. pneumoniae by acting not as enzyme inhibitors but as cellular poisons, with sparfloxacin killing preferentially through gyrases and ciprofloxACin through topoisomersase IV. Expand
Quinolone resistance mutations in topoisomerase IV: relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus
TLDR
Findings provide direct genetic evidence that topoisomersase IV is the primary target of current fluoroquinolones in S. aureus and that this effect may result from the greater sensitivity of topoisomerase IV relative to that of DNA gyrase to these agents. Expand
Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus
TLDR
It is demonstrated that mutations in gyrA or mutations leading to reduced drug accumulation occur after alteration of GrlA, supporting the previous findings that DNA topoisomerase IV is a primary target of fluoroquinolones in S. aureus. Expand
Characteristics of quinolone-induced small colony variants in Staphylococcus aureus.
TLDR
Pazufloxacin-induced SCVs represent a mutant that one might expect to be rapidly eliminated in vivo and, hence, not to survive as a quinolone-resistant pathogen, and suggests a novel approach for development of futureQuinolones. Expand
Mutations in Topoisomerase IV and DNA Gyrase of Staphylococcus aureus: Novel Pleiotropic Effects on Quinolone and Coumarin Activity
TLDR
The findings indicate that alterations in topoisomerases may have pleiotropic effects on different classes of inhibitors as well as on inhibitors within the same class. Expand
A novel, double mutation in DNA gyrase A of Escherichia coli conferring resistance to quinolone antibiotics
TLDR
It is hypothesized that some amino acids within the quinolone resistance-determining region of gyrase A are more important for the association of subunits rather than for the activity of the holoenzyme. Expand
Antibacterial Activity of Gatifloxacin (AM-1155, CG5501, BMS-206584), a Newly Developed Fluoroquinolone, against Sequentially Acquired Quinolone-Resistant Mutants and thenorA Transformant of Staphylococcus aureus
  • Hideyuki Fukuda, S. Hori, K. Hiramatsu
  • Medicine, Biology
  • Antimicrobial Agents and Chemotherapy
  • 1998
TLDR
Gatifloxacin possessed potent activity against the NorA-overproducing strain S. aureus NY12, thenorA transformant, which was slightly lower than that against the parent strain SA113, and the increases in the MICs of the quinolones tested against NY12 were negatively correlated with the hydrophobicity of thequinolones (correlation coefficient, −0.93;P < 0.01). Expand
A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly
TLDR
A defect in the electron transport system allows S. aureus SCVs to resist aminoglycosides and persist intracellularly, and this observation as well as other biochemical characteristics of SCVs suggests a link between electron-transport-defective strains and persistent infections. Expand
Engineering the Specificity of Antibacterial Fluoroquinolones: Benzenesulfonamide Modifications at C-7 of Ciprofloxacin Change Its Primary Target in Streptococcus pneumoniae from Topoisomerase IV to Gyrase
TLDR
Data show unequivocally that the C-7 substituent determines not only the potency but also the target preference of fluoroquinolones, which supports one key postulate of the Shen model of quinolone action. Expand
DNA Gyrase and Topoisomerase IV Are Dual Targets of Clinafloxacin Action in Streptococcus pneumoniae
  • Xiao-Su Pan, L. Fisher
  • Biology, Medicine
  • Antimicrobial Agents and Chemotherapy
  • 1998
TLDR
The results suggested that clinafloxacin displays comparable if unequal targeting of gyrase and topoisomerase IV and its first- and second-step mutants are desirable features in limiting the emergence of bacterial resistance. Expand
...
1
2
3
4
5
...