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 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 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 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 Alteration in the GyrA Subunit of DNA Gyrase and the ParC Subunit of DNA Topoisomerase IV in Quinolone-Resistant Clinical Isolates ofStaphylococcus epidermidis

1998 ◽  
Vol 42 (12) ◽  
pp. 3293-3295 ◽  
Author(s):  
Zhiyu Li ◽  
Takashi Deguchi ◽  
Mitsuru Yasuda ◽  
Takeshi Kawamura ◽  
Emiko Kanematsu ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Dna Gyrase ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Simultaneous Presence ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
High Level

ABSTRACT We examined 22 clinical isolates of Staphylococcus epidermidis to analyze the association of alterations in GyrA and ParC with fluoroquinolone resistance. The simultaneous presence of GyrA and ParC alterations was associated with a high level of fluoroquinolone resistance in the clinical isolates of S. epidermidis.

scholarly journals Alterations in the GyrA Subunit of DNA Gyrase and the ParC Subunit of DNA Topoisomerase IV Associated with Quinolone Resistance in Enterococcus faecalis

1998 ◽  
Vol 42 (2) ◽  
pp. 433-435 ◽  
Author(s):  
Emiko Kanematsu ◽  
Takashi Deguchi ◽  
Mitsuru Yasuda ◽  
Takeshi Kawamura ◽  
Yoshinori Nishino ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Primary Target ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
High Level

ABSTRACT The gyrA and parC genes of 31 clinical isolates of Enterococcus faecalis, including fluoroquinolone-resistant isolates, were partially sequenced and analyzed for target alterations. Topoisomerase IV may be a primary target in E. faecalis, but high-level fluoroquinolone resistance was associated with simultaneous alterations in both GyrA and ParC.

scholarly journals In Vitro Characterization of the Antibacterial Spectrum of Novel Bacterial Type II Topoisomerase Inhibitors of the Aminobenzimidazole Class

2006 ◽  
Vol 50 (4) ◽  
pp. 1228-1237 ◽  
Author(s):  
Nagraj Mani ◽  
Christian H. Gross ◽  
Jonathan D. Parsons ◽  
Brian Hanzelka ◽  
Ute Müh ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Wide Spectrum ◽  
Dna Gyrase ◽  
Antibacterial Activities ◽  
Mechanisms Of Action ◽  
Fluoroquinolone Resistance ◽  
Topoisomerase Iv ◽  
Low Frequencies

ABSTRACT Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities.

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.

scholarly journals Topoisomerase Mutations in Fluoroquinolone-Resistant and Methicillin-Susceptible and -Resistant Clinical Isolates of Staphylococcus aureus

1998 ◽  
Vol 42 (1) ◽  
pp. 197-198 ◽  
Author(s):  
Glenn W. Kaatz ◽  
Susan M. Seo
Keyword(s):  
Staphylococcus Aureus ◽  
Restriction Fragment Length Polymorphism ◽  
Fragment Length Polymorphism ◽  
Dna Gyrase ◽  
Clinical Isolates ◽  
Polymorphism Analysis ◽  
Topoisomerase Iv ◽  
Genes Encoding ◽  
Resistant Strains ◽  
Restriction Fragment Length

ABSTRACT The incidence of the various mutations in the genes encoding topoisomerase IV and DNA gyrase in fluoroquinolone-resistant clinical isolates of Staphylococcus aureus is not known. Using restriction fragment length polymorphism analysis and DNA sequencing, we found that in fluoroquinolone- and methicillin-resistant strains, mutations in grlA and gyrA are quite likely to be present together. For fluoroquinolone-resistant but methicillin-susceptible strains, mutations in grlA alone are more common.

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