scholarly journals Transferable Quinolone Resistance in Vibrio cholerae

2009 ◽  
Vol 54 (2) ◽  
pp. 799-803 ◽  
Author(s):  
Hong Bin Kim ◽  
Minghua Wang ◽  
Sabeena Ahmed ◽  
Chi Hye Park ◽  
Regina C. LaRocque ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Vibrio Cholerae ◽  
Dna Gyrase ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
A Subunit ◽  
Resistant Strains ◽  
Over Time

ABSTRACT Ciprofloxacin was introduced for treatment of patients with cholera in Bangladesh because of resistance to other agents, but its utility has been compromised by the decreasing ciprofloxacin susceptibility of Vibrio cholerae over time. We correlated levels of susceptibility and temporal patterns with the occurrence of mutation in gyrA, which encodes a subunit of DNA gyrase, followed by mutation in parC, which encodes a subunit of DNA topoisomerase IV. We found that ciprofloxacin activity was more recently further compromised in strains containing qnrVC3, which encodes a pentapeptide repeat protein of the Qnr subfamily, members of which protect topoisomerases from quinolone action. We show that qnrVC3 confers transferable low-level quinolone resistance and is present within a member of the SXT integrating conjugative element family found commonly on the chromosomes of multidrug-resistant strains of V. cholerae and on the chromosomes of Escherichia coli transconjugants constructed in the laboratory. Thus, progressive increases in quinolone resistance in V. cholerae are linked to cumulative mutations in quinolone targets and most recently to a qnr gene on a mobile multidrug resistance element, resulting in further challenges for the antimicrobial therapy of cholera.

scholarly journals Quinolone-resistant mutants of escherichia coli DNA topoisomerase IV parC gene.

1996 ◽  
Vol 40 (3) ◽  
pp. 710-714 ◽  
Author(s):  
Y Kumagai ◽  
J I Kato ◽  
K Hoshino ◽  
T Akasaka ◽  
K Sato ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Gyrase ◽  
Mutant Gene ◽  
Missense Mutations ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
E Coli ◽  
A Subunit ◽  
Resistant Strains ◽  
Mutant Genes

Escherichia coli quinolone-resistant strains with mutations of the parC gene, which codes for a subunit of topoisomerase IV, were isolated from a quinolone-resistant gyrA mutant of DNA gyrase. Quinolone-resistant parC mutants were also identified among the quinolone-resistant clinical strains. The parC mutants became susceptible to quinolones by introduction of a parC+ plasmid. Introduction of the multicopy plasmids carrying the quinolone-resistant parC mutant gene resulted in an increase in MICs of quinolones for the parC+ and quinolone-resistant gyrA strain. Nucleotide sequences of the quinolone-resistant parC mutant genes were determined, and missense mutations at position Gly-78, Ser-80, or Glu-84, corresponding to those in the quinolone-resistance-determining region of DNA gyrase, were identified. These results indicate that topoisomerase IV is a target of quinolones in E. coli and suggest that the susceptibility of E. coli cells to quinolones is determined by sensitivity of the targets, DNA gyrase and topoisomerase IV.

scholarly journals Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5662
Author(s):  
Natassja G. Bush ◽  
Isabel Diez-Santos ◽  
Lauren R. Abbott ◽  
Anthony Maxwell
Keyword(s):  
Cell Death ◽  
Antibiotic Resistance ◽  
Dna Gyrase ◽  
Mechanisms Of Action ◽  
Quinolone Resistance ◽  
Topoisomerase Iv ◽  
Bacterial Enzymes ◽  
Dna Topoisomerase ◽  
Quinolone Antibiotics ◽  
Dna Complex

Fluoroquinolones (FQs) are arguably among the most successful antibiotics of recent times. They have enjoyed over 30 years of clinical usage and become essential tools in the armoury of clinical treatments. FQs target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, where they stabilise a covalent enzyme-DNA complex in which the DNA is cleaved in both strands. This leads to cell death and turns out to be a very effective way of killing bacteria. However, resistance to FQs is increasingly problematic, and alternative compounds are urgently needed. Here, we review the mechanisms of action of FQs and discuss the potential pathways leading to cell death. We also discuss quinolone resistance and how quinolone treatment can lead to resistance to non-quinolone antibiotics.

Topoisomerase Sequences of Coagulase-Negative Staphylococcal Isolates Resistant to Ciprofloxacin or Trovafloxacin

1999 ◽  
Vol 43 (7) ◽  
pp. 1631-1637 ◽  
Author(s):  
Donald T. Dubin ◽  
Joseph E. Fitzgibbon ◽  
Massoumeh D. Nahvi ◽  
Joseph F. John
Keyword(s):  
Dna Gyrase ◽  
Fluoroquinolone Resistance ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Methicillin Resistant ◽  
Intraspecies Variation ◽  
Rrna Sequencing ◽  
Identification Of Species ◽  
Resistant Strains ◽  
Ciprofloxacin Resistance

ABSTRACT Coagulase-negative staphylococcal isolates (n = 188) were screened for susceptibility to oxacillin, ciprofloxacin, and trovafloxacin, a new fluoroquinolone. At an oxacillin concentration of ≥4 μg/ml, 43% were methicillin resistant; of these, 70% were ciprofloxacin resistant (MIC, ≥4 μg/ml). Of the methicillin-resistant, ciprofloxacin-resistant isolates, 46% were susceptible to ≤2 μg of trovafloxacin per ml and 32% were susceptible to ≤1 μg of trovafloxacin per ml. Sixteen isolates, including twelve that expressed fluoroquinolone resistance, were chosen for detailed analysis. Identification of species by rRNA sequencing revealed a preponderance of Staphylococcus haemolyticus andS. hominis among fluoroquinolone-resistant strains. Segments of genes (gyrA and grlA) encoding DNA gyrase and DNA topoisomerase IV were sequenced. Considerable interspecies variation was noted, mainly involving noncoding nucleotide changes. Intraspecies variation consisted of coding changes associated with fluoroquinolone resistance. As for S. aureus, ciprofloxacin resistance (MIC, ≥8 μg/ml) and increased trovafloxacin MICs (0.25 to 2 μg/ml) could be conferred by the combined presence of single mutations in each gyrA and grlA gene. Trovafloxacin MICs of ≥8 μg/ml also occurred, but these required an additional mutation in grlA.

scholarly journals Topoisomerase Mutations in Trovafloxacin-ResistantStaphylococcus aureus

1998 ◽  
Vol 42 (8) ◽  
pp. 2122-2124 ◽  
Author(s):  
Joseph E. Fitzgibbon ◽  
Joseph F. John ◽  
Jennifer L. Delucia ◽  
Donald T. Dubin
Keyword(s):  
Staphylococcus Aureus ◽  
Resistance Mutations ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Methicillin Resistant ◽  
A Subunit ◽  
Resistant Strains

ABSTRACT A total of 201 Staphylococcus aureus isolates were surveyed for susceptibility to ciprofloxacin and trovafloxacin. Of 66 methicillin-resistant isolates, 89% were ciprofloxacin resistant and 6% were also trovafloxacin resistant. Trovafloxacin-resistant strains had unusual patterns of quinoline resistance mutations in DNA topoisomerase genes, including two mutations in the A subunit (encoded by grlA) of topoisomerase IV.

scholarly journals DNA Sequence Analysis of DNA Gyrase and DNA Topoisomerase IV Quinolone Resistance-Determining Regions of Salmonella enterica Serovar Typhi and Serovar Paratyphi A

2002 ◽  
Vol 46 (10) ◽  
pp. 3249-3252 ◽  
Author(s):  
Kenji Hirose ◽  
Ai Hashimoto ◽  
Kazumichi Tamura ◽  
Yoshiaki Kawamura ◽  
Takayuki Ezaki ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Dna Sequence ◽  
Salmonella Enterica ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Single Mutation ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Salmonella Enterica Serovar Typhi

ABSTRACT The mutations that are responsible for fluoroquinolone resistance in the gyrA, gyrB, parC, and parE genes of Salmonella enterica serovar Typhi and serovar Paratyphi A were investigated. The sequences of the quinolone resistance-determining region of the gyrA gene in clinical isolates which showed decreased susceptibilities to fluoroquinolones had a single mutation at either the Ser-83 or the Asp-87 codon, and no mutations were found in the gyrB, parC, and parE genes.

scholarly journals Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1157-1163 ◽  
Author(s):  
J Yamagishi ◽  
T Kojima ◽  
Y Oyamada ◽  
K Fujimoto ◽  
H Hattori ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gene Dosage ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Wild Type Allele ◽  
Wild Type ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Transformation Experiment ◽  
Dna Fragment

A 4.2-kb DNA fragment conferring quinolone resistance was cloned from a quinolone-resistant clinical isolate of Staphylococcus aureus and was shown to possess a part of the grlB gene and a mutated grlA gene. S-80-->F and E-84-->K mutations in the grlA gene product were responsible for the quinolone resistance. The mutated grlA genes responsible for quinolone resistance were dominant over the wild-type allele, irrespective of gene dosage in a transformation experiment with the grlA gene alone. However, dominance by mutated grlA genes depended on gene dosage when bacteria were transformed with the grlA and grlB genes in combination. Quinolone-resistant gyrA mutants were easily isolated from a strain, S. aureus RN4220, carrying a plasmid with the mutated grlA gene, though this was not the case for other S. aureus strains lacking the plasmid. The elimination of this plasmid from such quinolone-resistant gyrA mutants resulted in marked increases in quinolone susceptibility. These results suggest that both DNA gyrase and DNA topoisomerase IV may be targets of quinolones and that the quinolone susceptibility of organisms may be determined by which of these enzymes is most quinolone sensitive.

scholarly journals Interaction of the Plasmid-Encoded Quinolone Resistance Protein QnrA with Escherichia coli Topoisomerase IV

2005 ◽  
Vol 49 (7) ◽  
pp. 3050-3052 ◽  
Author(s):  
John H. Tran ◽  
George A. Jacoby ◽  
David C. Hooper
Keyword(s):  
Escherichia Coli ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Topoisomerase Iv ◽  
Displacement Assay ◽  
Resistance Protein

ABSTRACT Purified QnrA blocked ciprofloxacin inhibition of topoisomerase IV, just as QnrA was previously found to prevent quinolone inhibition of DNA gyrase. With a gel displacement assay, tagged QnrA was shown to bind to topoisomerase IV and its subunits in a reaction that did not depend on the presence of DNA, quinolone, or ATP.

Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones.

1997 ◽  
Vol 41 (2) ◽  
pp. 471-474 ◽  
Author(s):  
X S Pan ◽  
L M Fisher
Keyword(s):  
Escherichia Coli ◽  
Streptococcus Pneumoniae ◽  
Hot Spot ◽  
Dna Gyrase ◽  
Second Step ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Selective Targeting

gyrA and parC mutations have been identified inn Streptococcus pneumoniae mutants stepwise selected for resistance to sparfloxacin, an antipneumococcal fluoroquinolone. GyrA mutations (at the position equivalent to resistance hot spot Ser-83 in Escherichia coli GyrA) were found in all 17 first-step mutants examined and preceded DNA topoisomerase IV parC mutations (at Ser-79 or Glu-83), which appeared only in second-step mutants. The targeting of gyrase by sparfloxacin in S. pneumoniae but of topoisomerase IV by ciprofloxacin indicates that target preference can be altered by changes in quinolone structure.

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