ArticleAntimicrobial agents and chemotherapy2005
Novel Ser79Leu and Ser81Ile substitutions in the quinolone resistance-determining regions of ParC topoisomerase IV and GyrA DNA gyrase subunits from recent fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Novel Bacterial Topoisomerase Inhibitors: A New Front in an Old War.Journal of molecular biology · 2026Review
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Polymorphism and mutational diversity of virulence (vcgCPI/vcgCPE) and resistance determinants (aac(3)-IIa, (aacC2, strA, Sul 1, and 11) among human pathogenic Vibrio species recovered from surface waters in South-Western districts of Uganda.Journal, genetic engineering & biotechnology · 2023Article
- Emergence of a ST248Infection and drug resistance · 2023Article
- In vitro antibacterial activities of JNJ-Q2, a new broad-spectrum fluoroquinolone.Antimicrobial agents and chemotherapy · 2010Article
- Characterization of the quinolone resistant determining regions in clinical isolates of pneumococci collected in Canada.Annals of clinical microbiology and antimicrobials · 2010Article
- Fluoroquinolone-resistant Streptococcus pneumoniae.Emerging infectious diseases · 2006Article
- Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents.Antimicrobial agents and chemotherapy · 2006Article
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3 authors at 1 institution in 1 country.
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Abstract
Resistance of Streptococcus pneumoniae to fluoroquinolones is caused predominantly by amino acid substitutions at positions Ser79 of ParC and Ser81 of GyrA to either Phe or Tyr encoded in the quinolone resistance-determining regions of the parC topoisomerase IV and gyrA DNA gyrase genes. Analysis of highly resistant clinical isolates identified novel second-step substitutions, Ser79Leu (ParC) and Ser81Ile (GyrA). To determine contributions of these new mutations to fluoroquinolone resistance either alone or in combination with other Ser79/81 alleles, the substitutions Ser79Leu/Phe/Tyr in ParC and Ser81Ile/Phe/Tyr in GyrA were introduced into the R6 background, resulting in 15 isogenic strains. Their level of fluoroquinolone resistance was determined by susceptibility testing for ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, gemifloxacin, garenoxacin, and norfloxacin. Leu79 and Ile81 alone as well as 79/81Phe/Tyr substitutions did not contribute significantly to resistance, with fluoroquinolone MICs increasing two- to fourfold compared to wild type for all agents tested. Fluoroquinolone MICs for double transformants ParC Ser79Phe/Tyr/Leu-GyrA Ser81Phe/Tyr were uniformly increased by 8- to 64-fold regardless of pairs of amino acid substitutions. However, combinations including Ile81 conferred two- to fourfold-higher levels of resistance than did combinations including any other Ser81 GyrA substitution, thus demonstrating the differential effects of diverse amino acid substitutions at particular hotspots on fluoroquinolone MICs.
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