scholarly journals Fluoroquinolone Resistance Is a Poor Surrogate Marker for Type II Topoisomerase Mutations in Clinical Isolates of Streptococcus pneumoniae

2001 ◽  
Vol 39 (7) ◽  
pp. 2719-2721 ◽  
Author(s):  
J. J. Millichap ◽  
E. Pestova ◽  
F. Siddiqui ◽  
G. A. Noskin ◽  
L. R. Peterson
2001 ◽  
Vol 45 (9) ◽  
pp. 2631-2634 ◽  
Author(s):  
Darrin J. Bast ◽  
Joyce C. S. de Azavedo ◽  
Tiffany Y. Tam ◽  
Laurie Kilburn ◽  
Carla Duncan ◽  
...  

ABSTRACT Analysis of 71 ciprofloxacin-resistant (MIC ≥ 4 μg/ml)Streptococcus pneumoniae clinical isolates revealed only 1 for which the quinolone resistance-determining regions of theparC, parE, and gyrB genes were genetically related to those of viridans group streptococci. Our findings support the occurrence of interspecies recombination of type II topoisomerase genes; however, its contribution to the emergence of quinolone resistance among pneumococci appears to have been minimal.


2007 ◽  
Vol 51 (7) ◽  
pp. 2625-2627 ◽  
Author(s):  
Jeong Hwan Shin ◽  
Hee Jung Jung ◽  
Hye Ran Kim ◽  
Joseph Jeong ◽  
Seok Hoon Jeong ◽  
...  

ABSTRACT The genes erm(B), mef(A), and both erm(B) and mef(A) were identified in 42.6, 10.1, and 47.3%, respectively, of the erythromycin-resistant Streptococcus pneumoniae isolates. Of the strains, 3.8% were nonsusceptible to levofloxacin and had 1 to 6 amino acid changes in the quinolone resistance-determining region, including a new mutation, Asn94Ser, in the product of parC. Levofloxacin with reserpine was highly specific for efflux screening.


2005 ◽  
Vol 49 (6) ◽  
pp. 2479-2486 ◽  
Author(s):  
Nataliya Korzheva ◽  
Todd A. Davies ◽  
Raul Goldschmidt

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.


2005 ◽  
Vol 49 (2) ◽  
pp. 779-780 ◽  
Author(s):  
Mathias W. R. Pletz ◽  
Lesley McGee ◽  
Bernard Beall ◽  
Cynthia G. Whitney ◽  
Keith P. Klugman

ABSTRACT Mutations in the topoisomerase type II enzymes account for fluoroquinolone resistance in Streptococcus pneumoniae. These mutations can arise spontaneously or be transferred by intraspecies or interspecies recombination, primarily with viridans streptococci. We analyzed the nucleotide sequences of the quinolone resistance-determining regions of 49 invasive levofloxacin-resistant pneumococcal isolates and did not find any evidence for interspecies recombination.


2000 ◽  
Vol 44 (11) ◽  
pp. 3049-3054 ◽  
Author(s):  
Darrin J. Bast ◽  
Donald E. Low ◽  
Carla L. Duncan ◽  
Laurie Kilburn ◽  
Lionel A. Mandell ◽  
...  

ABSTRACT We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates ofS. pneumoniae for which the ciprofloxacin MIC is ≥4 μg/ml and 28 isolates for which the ciprofloxacin MIC is ≤2 μg/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 μg/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 μg/ml) and high-level (MICs, 64 μg/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.


2005 ◽  
Vol 49 (2) ◽  
pp. 846-848 ◽  
Author(s):  
Heather J. Smith-Adam ◽  
Kimberly A. Nichol ◽  
Daryl J. Hoban ◽  
George G. Zhanel

ABSTRACT The stability of fluoroquinolone resistance in Streptococcus pneumoniae was evaluated in laboratory-derived mutants and clinical isolates. Isolates with various genotypes and phenotypes were subcultured for 20 days on antibiotic-free media and were monitored by E-tests to identify any alterations in resistance. Fluoroquinolone resistance mechanisms, whether efflux or chromosomally mediated, remained stable in both clinical and laboratory-derived mutants.


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