The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae
Open accessAbstract
Ciprofloxacin-resistant mutants of Streptococcus pneumoniae 7785 were generated by stepwise selection at increasing drug concentrations. Sequence analysis of PCR products from the strains was used to examine the quinolone resistance-determining regions of the GyrA and GyrB proteins of DNA gyrase and the analogous regions of the ParC and ParE subunits of DNA topoisomerase IV. First-step mutants exhibiting low-level resistance had no detectable changes in their topoisomerase quinolone resistance-determining regions, suggesting altered permeation or another novel resistance mechanism. Nine of 10 second-step mutants exhibited an alteration in ParC at Ser-79 to Tyr or Phe or at Ala-84 to Thr. Third- and fourth-step mutants displaying high-level ciprofloxacin resistance were found to have, in addition to the ParC alteration, a change in GyrA at residues equivalent to Escherichia coli GyrA resistance hot spots Ser-83 and Asp-87 or in GyrB at Asp-435 to Asn, equivalent to E. coli Asp-426, part of a highly conserved EGDSA motif in GyrB. No ParE changes were observed. Complementary analysis of two S. pneumoniae clinical isolates displaying low-level resistance to ciprofloxacin revealed a ParC change at Ser-79 to Phe or Arg-95 to Cys but no changes in GyrA, GyrB, or ParE. A highly resistant isolate, in addition to a ParC mutation, had a GyrA alteration at the residue equivalent to E. coli Asp-87. Thus, in both laboratory strains and clinical isolates, ParC mutations preceded those in GyrA, suggesting that topoisomerase IV is a primary topoisomerase target and gyrase is a secondary target for ciprofloxacin in S. pneumoniae.
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Cites
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Cited by
DNA gyrase, topoisomerase IV, and the 4-quinolones.
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Mechanism of Quinolone Action and Resistance
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Increasing Prevalence of Multidrug-Resistant Streptococcus pneumoniae in the United States
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Metadata
- Authors
- Pan, X. S., Ambler, J., Mehtar, S., & Fisher, L. M.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1996-10
- Volume
- 40
- Issue
- 10
- Pages
- 2321-2326
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- OpenAlex
- W2107131874
- Cited by
- 437
- References
- 20
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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