scholarly journals Interspecies Recombination Contributes Minimally to Fluoroquinolone Resistance in Streptococcus pneumoniae

2001 ◽  
Vol 45 (9) ◽  
pp. 2631-2634 ◽  
Author(s):  
Darrin J. Bast ◽  
Joyce C. S. de Azavedo ◽  
Tiffany Y. Tam ◽  
Laurie Kilburn ◽  
Carla Duncan ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Type Ii ◽  
Viridans Group Streptococci ◽  
Interspecies Recombination

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.

scholarly journals Interspecies Recombination in Type II Topoisomerase Genes Is Not a Major Cause of Fluoroquinolone Resistance in Invasive Streptococcus pneumoniae Isolates in the United States

2005 ◽  
Vol 49 (2) ◽  
pp. 779-780 ◽  
Author(s):  
Mathias W. R. Pletz ◽  
Lesley McGee ◽  
Bernard Beall ◽  
Cynthia G. Whitney ◽  
Keith P. Klugman
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
The United States ◽  
Nucleotide Sequences ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Type Ii ◽  
Viridans Streptococci ◽  
Interspecies Recombination

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.

scholarly journals Prevalence, Characteristics, and Molecular Epidemiology of Macrolide and Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae at Five Tertiary-Care Hospitals in Korea

2007 ◽  
Vol 51 (7) ◽  
pp. 2625-2627 ◽  
Author(s):  
Jeong Hwan Shin ◽  
Hee Jung Jung ◽  
Hye Ran Kim ◽  
Joseph Jeong ◽  
Seok Hoon Jeong ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Amino Acid ◽  
Molecular Epidemiology ◽  
Tertiary Care ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
New Mutation ◽  
Tertiary Care Hospitals

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.

scholarly journals 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

2005 ◽  
Vol 49 (6) ◽  
pp. 2479-2486 ◽  
Author(s):  
Nataliya Korzheva ◽  
Todd A. Davies ◽  
Raul Goldschmidt
Keyword(s):  
Streptococcus Pneumoniae ◽  
Amino Acid ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Amino Acid Substitutions ◽  
Topoisomerase Iv ◽  
Isogenic Strains ◽  
New Mutations

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.

scholarly journals Interspecies Recombination Occurs Frequently in Quinolone Resistance-Determining Regions of Clinical Isolates of Streptococcus pyogenes

2008 ◽  
Vol 52 (11) ◽  
pp. 4191-4193 ◽  
Author(s):  
Christoph B. Duesberg ◽  
Surbhi Malhotra-Kumar ◽  
Herman Goossens ◽  
Lesley McGee ◽  
Keith P. Klugman ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Streptococcus Pyogenes ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Surveillance Study ◽  
Fluoroquinolone Resistance ◽  
Interspecies Recombination

ABSTRACT Fluoroquinolone resistance in Streptococcus pyogenes has been reported only anecdotally, but a recent Belgian surveillance study found a rate of nonsusceptibility of 5.4%. From an analysis of these isolates, we show that interspecies horizontal gene transfer within the parC quinolone resistance-determining region is a frequent phenomenon that might contribute to fluoroquinolone resistance.

scholarly journals Molecular Evolution Perspectives on Intraspecific Lateral DNA Transfer of Topoisomerase and Gyrase Loci in Streptococcus pneumoniae, with Implications for Fluoroquinolone Resistance Development and Spread

2005 ◽  
Vol 49 (10) ◽  
pp. 4315-4326 ◽  
Author(s):  
Michael J. Stanhope ◽  
Stacey L. Walsh ◽  
Julie A. Becker ◽  
Michael J. Italia ◽  
Karen A. Ingraham ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Dna Transfer ◽  
Lateral Transfer ◽  
Respiratory Pathogen ◽  
Fluoroquinolone Resistance ◽  
Data Set ◽  
History Of ◽  
Important Means ◽  
Viridans Group Streptococci

ABSTRACT Fluoroquinolones are an important class of antibiotics for the treatment of infections arising from the gram-positive respiratory pathogen Streptococcus pneumoniae. Although there is evidence supporting interspecific lateral DNA transfer of fluoroquinolone target loci, no studies have specifically been designed to assess the role of intraspecific lateral transfer of these genes in the spread of fluoroquinolone resistance. This study involves a comparative evolutionary perspective, in which the evolutionary history of a diverse set of S. pneumoniae clinical isolates is reconstructed from an expanded multilocus sequence typing data set, with putative recombinants excluded. This control history is then assessed against networks of each of the four fluoroquinolone target loci from the same isolates. The results indicate that although the majority of fluoroquinolone target loci from this set of 60 isolates are consistent with a clonal dissemination hypothesis, 3 to 10% of the sequences are consistent with an intraspecific lateral transfer hypothesis. Also evident were examples of interspecific transfer, with two isolates possessing a parE-parC gene region arising from viridans group streptococci. The Spain 23F-1 clone is the most dominant fluoroquinolone-nonsusceptible clone in this set of isolates, and the analysis suggests that its members act as frequent donors of fluoroquinolone-nonsusceptible loci. Although the majority of fluoroquinolone target gene sequences in this set of isolates can be explained on the basis of clonal dissemination, a significant number are more parsimoniously explained by intraspecific lateral DNA transfer, and in situations of high S. pneumoniae population density, such events could be an important means of resistance spread.

scholarly journals Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro.

1996 ◽  
Vol 40 (11) ◽  
pp. 2505-2510 ◽  
Author(s):  
J Tankovic ◽  
B Perichon ◽  
J Duval ◽  
P Courvalin
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gene Amplification ◽  
Low Frequency ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Primary Target ◽  
Total Dna

We have analyzed by gene amplification and sequencing mutations in the quinolone resistance-determining regions of the gyrA, gyrB, and parC genes of fluoroquinolone-resistant Streptococcus pneumoniae mutants obtained during therapy or in vitro. Mutations leading to substitutions in ParC were detected in the two mutants obtained in vivo, BM4203-R (substitution of a histidine for an aspartate at position 84 [Asp-84-->His]; Staphylococcus aureus coordinates) and BM4204-R (Ser-80-->Phe), and in two mutants obtained in vitro (Ser-80-->Tyr). An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-->Phe change. We could not detect any mutation in the three remaining mutants obtained in vitro. Total DNA from BM4203-R, BM4204-R, and BM4205-R3 was used to transform S. pneumoniae CP1000 by selection on fluoroquinolones. For the parC mutants, transformants with phenotypes indistinguishable from those of the donors were obtained at frequencies (5 x 10(-3) to 8 x 10(-3)) compatible with monogenic transformation. By contrast, transformants were obtained at a low frequency (4 x 10(-5)), compatible with the transformation of two independent genes, for the gyrA mutant. Resistant transformants of CP1000 were also obtained with an amplified fragment of parC from BM4203-R and BM4204-R but not with a gyrA fragment from BM4205-R3. All transformants had mutations identical to those in the donors. These data strongly suggest that ParC is the primary target for fluoroquinolones in S. pneumoniae and that BM4205-R3 is resistant to higher levels of the drugs following the acquisition of two mutations, including one in gyrA.

scholarly journals In Vitro Activities of Garenoxacin (BMS-284756) against Streptococcus pneumoniae, Viridans Group Streptococci, and Enterococcus faecalis Compared to Those of Six Other Quinolones

2003 ◽  
Vol 47 (11) ◽  
pp. 3542-3547 ◽  
Author(s):  
Patrick Grohs ◽  
Serge Houssaye ◽  
Agnès Aubert ◽  
Laurent Gutmann ◽  
Emmanuelle Varon
Keyword(s):  
Streptococcus Pneumoniae ◽  
Enterococcus Faecalis ◽  
Bactericidal Effect ◽  
Clinical Isolates ◽  
Active Efflux ◽  
Resistant Strains ◽  
Different Strains ◽  
Viridans Group Streptococci ◽  
Derivatives Of

ABSTRACT The activity of garenoxacin, a new quinolone, was determined in comparison with other quinolones against different strains of S. pneumoniae, viridans group streptococci (VGS), and Enterococcus faecalis. Strains were quinolone-susceptible clinical isolates and quinolone-resistant strains with defined mechanisms of resistance obtained from either clinical isolates or derivatives of S. pneumoniae R6. Clinical quinolone-susceptible strains of S. pneumoniae, VGS and E. faecalis showed garenoxacin MICs within a range of 0.03 μg/ml to 0.25 μg/ml. Garenoxacin MICs increased two- to eightfold when one mutation was present in the ParC quinolone resistance-determining region (QRDR), fourfold when one mutation was present in the GyrA QRDR (S. pneumoniae), 8- to 64-fold when two or three mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two mutations were present in both the GyrA and ParC QRDRs (Streptococcus pneumoniae). Increased active efflux had a moderate effect on garenoxacin MICs for S. pneumoniae and VGS. Against S. pneumoniae, garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than by a single parC mutation. Although garenoxacin was generally two- to fourfold more active than moxifloxacin against the different wild-type or mutant strains of S. pneumoniae, VGS, and E. faecalis, it was two- to fourfold less active than gemifloxacin. At four times the respective MIC for each strain, the bactericidal effect of garenoxacin, observed at 6 h for S. pneumoniae and at 24 h for S. oralis and E. faecalis, was not influenced by the presence of mutation either in the ParC or in both the ParC and GyrA QRDRs.

scholarly journals Relationship between Mutations in the gyrA Gene and Quinolone Resistance in Clinical Isolates of Corynebacterium striatum and Corynebacterium amycolatum

2005 ◽  
Vol 49 (5) ◽  
pp. 1714-1719 ◽  
Author(s):  
Josep M. Sierra ◽  
Luis Martinez-Martinez ◽  
Fernando Vázquez ◽  
Ernest Giralt ◽  
Jordi Vila
Keyword(s):  
Amino Acid ◽  
Test Method ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Moderate Increase ◽  
Gyra Gene ◽  
Double Mutation ◽  
Corynebacterium Striatum

ABSTRACT Quinolone susceptibility was analyzed in 17 clinical isolates of Corynebacterium striatum and 9 strains of Corynebacterium amycolatum by the E-test method in Mueller-Hinton agar plates. The C. striatum ATCC 6940 strain was used as a control strain. The amplified quinolone resistance determining regions of the gyrA genes of C. amycolatum and C. striatum were characterized. Four in vitro quinolone-resistant mutants of C. amycolatum were selected and analyzed. Both in vivo and in vitro quinolone-resistant strains of C. amycolatum showed high levels of fluoroquinolone resistance in strains with a double mutation leading to an amino acid change in positions 87 and 91 or positions 87 and 88 (unusual mutation) of GyrA, whereas the same concomitant mutations at amino acid positions 87 and 91 in GyrA of C. striatum produced high levels of resistance to ciprofloxacin and levofloxacin but only showed a moderate increase in the MIC of moxifloxacin, suggesting that other mechanism(s) of quinolone resistance could be involved in moxifloxacin resistance in C. amycolatum. Moreover, a PCR-RFLP-NcoI of the gyrA gene was developed to distinguish between C. amycolatum and C. striatum species.

scholarly journals Comparative Analysis of Quinolone Resistance in Clinical Isolates ofKlebsiella pneumoniaeandEscherichia colifrom Chinese Children and Adults

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ying Huang ◽  
James O. Ogutu ◽  
Jiarui Gu ◽  
Fengshu Ding ◽  
Yuhong You ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Environmental Issues ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Chinese Adults ◽  
Double Mutation ◽  
History Of ◽  
Ciprofloxacin Resistance ◽  
Resistance Rates

The objective of this study was to compare quinolone resistance andgyrAmutations in clinical isolates ofKlebsiella pneumoniaeandEscherichia colifrom Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions ingyrAgene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types ofgyrAmutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (allP>0.05). The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P=0.5444). Children with no known history of quinolone administration were found to carry fluoroquinolone-resistantEnterobacteriaceaeisolates. The occurrence of ciprofloxacin resistance and the major types ofgyrAmutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

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