scholarly journals Impact of Amino Acid Substitutions in B Subunit of DNA Gyrase in Mycobacterium leprae on Fluoroquinolone Resistance

2012 ◽  
Vol 6 (10) ◽  
pp. e1838 ◽  
Author(s):  
Kazumasa Yokoyama ◽  
Hyun Kim ◽  
Tetsu Mukai ◽  
Masanori Matsuoka ◽  
Chie Nakajima ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mycobacterium Leprae ◽  
Dna Gyrase ◽  
Fluoroquinolone Resistance ◽  
Amino Acid Substitutions ◽  
B Subunit

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 Mutations in the gyrA, parC, and parE Genes Associated with Fluoroquinolone Resistance in Clinical Isolates of Mycoplasma hominis

1999 ◽  
Vol 43 (4) ◽  
pp. 954-956 ◽  
Author(s):  
Cécile M. Bebear ◽  
Joel Renaudin ◽  
Alain Charron ◽  
Hélène Renaudin ◽  
Bertille de Barbeyrac ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mycoplasma Hominis ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Amino Acid Substitutions ◽  
Topoisomerase Iv

ABSTRACT Five clinical isolates of Mycoplasma hominis from three different patients were examined for resistance to fluoroquinolones; some of these isolates were probably identical. All five isolates harbored amino acid substitutions in the quinolone resistance-determining regions of both DNA gyrase (GyrA) and topoisomerase IV (ParC or ParE). Furthermore, the novobiocin MIC for three isolates showed a significant increase. This is the first characterization of fluoroquinolone-resistant clinical mycoplasma isolates from humans.

scholarly journals Amino Acid Substitutions at Position 95 in GyrA Can Add Fluoroquinolone Resistance to Mycobacterium leprae

2011 ◽  
Vol 56 (2) ◽  
pp. 697-702 ◽  
Author(s):  
Kazumasa Yokoyama ◽  
Hyun Kim ◽  
Tetsu Mukai ◽  
Masanori Matsuoka ◽  
Chie Nakajima ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dna Cleavage ◽  
Recombinant Dna ◽  
Mycobacterium Leprae ◽  
Rapid Identification ◽  
Fluoroquinolone Resistance ◽  
Amino Acid Substitutions ◽  
Content Type ◽  
Cleavage Assay

ABSTRACTAmino acid substitutions at position 89 or 91 in GyrA of fluoroquinolone-resistantMycobacterium lepraeclinical isolates have been reported. In contrast, those at position 94 inM. tuberculosis, equivalent to position 95 inM. leprae, have been identified most frequently. To verify the possible contribution of amino acid substitutions at position 95 inM. lepraeto fluoroquinolone resistance, we conducted anin vitroassay using wild-type and mutant recombinant DNA gyrases. Fluoroquinolone-mediated supercoiling activity inhibition assay and DNA cleavage assay revealed the potent contribution of an amino acid substitution of Asp to Gly or Asn at position 95 to fluoroquinolone resistance. These results suggested the possible future emergence of quinolone-resistantM. lepraeisolates with these amino acid substitutions and the usefulness of detecting these mutations for the rapid identification of fluoroquinolone resistance in leprosy.

scholarly journals DNA Gyrase-Mediated Natural Resistance to Fluoroquinolones in Ehrlichia spp

2001 ◽  
Vol 45 (7) ◽  
pp. 2098-2105 ◽  
Author(s):  
M. Maurin ◽  
C. Abergel ◽  
D. Raoult
Keyword(s):  
Amino Acid ◽  
Current Knowledge ◽  
Dna Gyrase ◽  
Natural Resistance ◽  
Fluoroquinolone Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Ehrlichia Phagocytophila ◽  
Resistant Species ◽  
Phylogenetic Cluster

ABSTRACT Fluoroquinolone susceptibility heterogeneity between variousEhrlichia species has been previously demonstrated. In gram-negative bacteria, resistance to fluoroquinolones most often corresponds to specific amino acid variations in a portion of the protein sequence of the A subunit of DNA gyrase (GyrA), referred to as the quinolone resistance-determining region (QRDR). We suspected a similar mechanism to be responsible for natural resistance in someEhrlichia species. To verify this hypothesis, we sequenced the entire gyrA gene of the quinolone-susceptible speciesEhrlichia sennetsu and designed specific primers to amplify and sequence the QRDR of four other Ehrlichia species as well as the closely related species Cowdria ruminantium. We identified in the fluoroquinolone-resistant species Ehrlichia chaffeensis and Ehrlichia canis a specific GyrA QRDR amino acid sequence, also present in C. ruminantium (whose susceptibility to fluoroquinolones remains unknown). These three species belong to a single phylogenetic cluster referred to as theE. canis genogroup. A different GyrA QRDR pattern, shared by the Ehrlichia species representatives of the E. sennetsu and Ehrlichia phagocytophila genogroups, was identified. Three of the four species tested are known to be susceptible to fluoroquinolones. A serine residue in position 83 (Escherichia coli numbering) in the susceptible species is replaced by an alanine residue in fluoroquinolone-resistant species. These results are consistent with the current knowledge on fluoroquinolone resistance in other gram-negative bacteria. They are indicative of a natural gyrase-mediated resistance to fluoroquinolones in the E. canis genogroup.

scholarly journals Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at an STI Clinic in Guangzhou, China, 2016-2018.

2020 ◽  
Author(s):  
Wujian Ke ◽  
Dongling Li ◽  
Lai Sze Tso ◽  
Ran Wei ◽  
Yinyuan Lan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antimicrobial Resistance ◽  
Fluoroquinolone Resistance ◽  
23S Rrna ◽  
Resistance Testing ◽  
Rrna Gene ◽  
Amino Acid Substitutions ◽  
Resistance Mutations ◽  
Topoisomerase Iv ◽  
Two Samples

Abstract Background Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China.Methods A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA).Results 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I).Conclusions The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.

scholarly journals Are All the DNA Gyrase Mutations Found in Mycobacterium leprae Clinical Strains Involved in Resistance to Fluoroquinolones?

2007 ◽  
Vol 52 (2) ◽  
pp. 745-747 ◽  
Author(s):  
Stéphanie Matrat ◽  
Emmanuelle Cambau ◽  
Vincent Jarlier ◽  
Alexandra Aubry
Keyword(s):  
Dna Cleavage ◽  
Mycobacterium Leprae ◽  
Dna Gyrase ◽  
Fluoroquinolone Resistance ◽  
Clinical Strains

ABSTRACT Mycobacterium leprae DNA gyrases carrying various mutations, previously described in clinical strains, were investigated for quinolone susceptibility by inhibition of supercoiling and DNA cleavage promotion. We demonstrated that the gyrA mutations leading to G89C or A91V confer fluoroquinolone resistance whereas the gyrB mutation leading to D205N does not.

scholarly journals Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at an STI Clinic in Guangzhou, China, 2016-2018.

2020 ◽  
Author(s):  
Wujian Ke ◽  
Dongling Li ◽  
Lai Sze Tso ◽  
Ran Wei ◽  
Yinyuan Lan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antimicrobial Resistance ◽  
Fluoroquinolone Resistance ◽  
23S Rrna ◽  
Resistance Testing ◽  
Rrna Gene ◽  
Amino Acid Substitutions ◽  
Resistance Mutations ◽  
Topoisomerase Iv ◽  
Two Samples

Abstract BackgroundAntimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China.MethodsA total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA).Results98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I).ConclusionsThe high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.

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