Mutations in the gyrA and parC genes of quinolone-resistant Neisseria gonorrhoeae isolates in India

Kulkarni, Shrikant; Bala, Manju; Sane, Suvarna; Pandey, Sudhanshu; Bhattacharya, Jayanta; Risbud, Arun

doi:10.1016/j.ijantimicag.2012.08.007

Cited by 14 publications

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“…It was either a D95N substitution or D95G but D95N was more frequently encountered all over India. Similar observations have been made by other workers 18 24 25 .…”

Section: Discussionsupporting

confidence: 92%

Exploring quinolone resistance-determining region in Neisseria gonorrhoeae isolates from across India

et al. 2017

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Background & objectives:Antimicrobial resistance in Neisseria gonorrhoeae, the causative agent of gonorrhoea, is a subject of worldwide attention. The present study was undertaken to examine the rates of ciprofloxacin resistance, to correlate mutations in gyrA and parC genes with the level of resistance and to look for a variation in mutation pattern, if any, in isolates from across the country.Methods:A total of 113 isolates of N. gonorrhoeae collected from sexually transmitted infection patients in six centres during November 2010 to October 2013 were investigated. Minimum inhibitory concentration (MIC) determination was done by E-test and results interpreted as per Calibrated Dichotomous Sensitivity criteria. DNA sequence analysis of gyrA and parC genes was done.Results:Of the 113 isolates, only three (2.6%) were susceptible whereas eight (7.07%) were less susceptible, 32 [28.3%, 95% confidence interval (CI): 20.4-37.6%] resistant (MIC 1-3 µg/ml) and 70 (61.9%, 95% CI: 52.2-70.7%) exhibited high-level resistance (HLR) (MIC ≥4 µg/ml) to ciprofloxacin. A S91F substitution in gyrA gene was demonstrated in all ciprofloxacin non-susceptible isolates. All resistant and HLR isolates had a double mutation in gyrA gene. However, only 5.7 per cent of HLR isolates showed double mutations in parC gene. One isolate (MIC 32 µg/ml) had a previously undescribed G85D substitution in the parC gene.Interpretation & conclusions:A S91F substitution in gyrA gene was seen in all non-susceptible isolates of N. gonorrhoeae. It may be used as a marker for ciprofloxacin resistance for molecular surveillance approaches to complement the culture-based methods.

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“…It was either a D95N substitution or D95G but D95N was more frequently encountered all over India. Similar observations have been made by other workers 18 24 25 .…”

Section: Discussionsupporting

confidence: 92%

Exploring quinolone resistance-determining region in Neisseria gonorrhoeae isolates from across India

et al. 2017

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“…Our genomic surveillance revealed a detailed picture of the distribution of AMR determinants and their relation to phenotypic antimicrobial susceptibility in a region of public health concern. The results particularly suggest that the simultaneous amino acid substitutions in GyrA 91 and 95 could be a marker of resistance to fluoroquinolones in this geographical region, in addition to other geographical regions such as the USA [ 17 ], Russia [ 59 ] and India [ 60 ] where a strong association between the substitutions in GyrA and fluoroquinolone resistance has been reported. The marker can be utilized for point-of-care diagnostic and AMR tests (POC-AMR), the importance of which has been shown for enabling prompt diagnosis and individualized treatment, and helping to combat the spread of AMR [ 61, 62 ].…”

Section: Discussionmentioning

confidence: 82%

Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages

et al. 2018

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The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85 % of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99 % sensitivity and 100 % specificity. Approximately 10 % showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide.

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“…gyrA mutations (S91F) were found universally, with many of the isolates containing additional mutations in the quinolone resistance determining regions of the gyrA and parC genes (Table 2), which confer a high level of resistance to fluoroquinolones (e.g., ciprofloxacin) [28,30,38]. The very high rate of fluoroquinolone resistance may be an indicator of the overuse and misuse of this class of antimicrobials in this region of the world, as caused by over-the-counter availability, unregulated and counterfeit medicines, self-medication or unqualified practitioners who prescribe a full range of treatments [49,50].…”

Section: Discussionmentioning

confidence: 99%

“…However, few isolates from this region have been examined and, in most cases, disc diffusion methods that do not reflect the exact MIC have been used for antimicrobial susceptibility testing rather than quality assured, internationally validated methods to determine the exact MIC. Furthermore, genetic antimicrobial resistance determinants, with the exception of determinants for ciprofloxacin resistance [38], have never been studied.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from India, Pakistan and Bhutan in 2007–2011

et al. 2013

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BackgroundKnowledge on antimicrobial drug resistance and genetic characteristics of Neisseria gonorrhoeae isolates circulating in India, Pakistan, and Bhutan is sorely lacking. In this paper, we describe the prevalence of antimicrobial resistance and molecular characteristics of N. gonorrhoeae isolates from India, Pakistan, and Bhutan in 2007–2011.MethodsAntimicrobial susceptibility and β-lactamase production were tested for 65 N. gonorrhoeae isolates from India (n=40), Pakistan (n=18) and Bhutan (n=7) using Etest methodology (eight antimicrobials) and nitrocefin solution, respectively. Resistance determinants, i.e. penA, mtrR, porB1b, gyrA, and parC, were sequenced. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology.ResultsThe highest resistance level was observed for ciprofloxacin (94%), followed by penicillin G (68%), erythromycin (62%), tetracycline (55%), and azithromycin (7.7%). All the isolates were susceptible to ceftriaxone, cefixime, and spectinomycin. Thirty-four (52%) of the isolates were producing β-lactamase. No penA mosaic alleles or A501-altered alleles of penicillin-binding protein 2 were identified. Forty-nine NG-MAST STs were identified, of which 42 STs have not been previously described worldwide.ConclusionsBased on this study, ceftriaxone, cefixime, and spectinomycin can be used as an empirical first-line therapy for gonorrhoea in India, Pakistan, and Bhutan, whereas ciprofloxacin, penicillin G, tetracycline, erythromycin, and azithromycin should not be. It is imperative to strengthen the laboratory infrastructure in this region, as well as to expand the phenotypic and genetic surveillance of antimicrobial resistance, emergence of new resistance, particularly, to extended-spectrum cephalosporins, and molecular epidemiology.

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Mutations in the gyrA and parC genes of quinolone-resistant Neisseria gonorrhoeae isolates in India

Cited by 14 publications

References 13 publications

Exploring quinolone resistance-determining region in Neisseria gonorrhoeae isolates from across India

Exploring quinolone resistance-determining region in Neisseria gonorrhoeae isolates from across India

Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages

Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from India, Pakistan and Bhutan in 2007–2011

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