Genotype analysis of ofloxacin-resistant multidrug-resistant
Adolescent
Adult
Antitubercular Agents
/ pharmacology
Drug Resistance, Multiple, Bacterial
/ genetics
Female
Genotype
Humans
India
/ epidemiology
Male
Microbial Sensitivity Tests
/ methods
Middle Aged
Mutation
/ drug effects
Mycobacterium tuberculosis
/ drug effects
Ofloxacin
/ pharmacology
Peptide Hydrolases
Polymerase Chain Reaction
/ methods
Tuberculosis, Multidrug-Resistant
/ drug therapy
Young Adult
Drug resistance
Mycobacterium tuberculosis
gyrase
multidrug-resistant tuberculosis
nitrate reductase assay
ofloxacin resistance
spoligotyping
Journal
The Indian journal of medical research
ISSN: 0971-5916
Titre abrégé: Indian J Med Res
Pays: India
ID NLM: 0374701
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
entrez:
29
5
2020
pubmed:
29
5
2020
medline:
4
3
2021
Statut:
ppublish
Résumé
Drug resistance surveillance offers useful information on trends of drug resistance and the efficacy of control measures. Studies and reports of drug-resistant mutations and phenotypic assays thus become important. This study was conducted to investigate the molecular characteristics of ofloxacin (OFX)-resistant, multidrug-resistant tuberculosis (MDR-TB) isolates from different geographical regions of India and their association with strains of different genotypes. Further, the nitrate reductase assay (NRA) was tested against Mycobacteria Growth Indicator Tube(MGIT) for the determination of OFX resistance as an alternative and cost-effective method. A total of 116 Mycobacterium tuberculosis isolates were used to assess the mutations in the gyrA, gyrB genes and resistance levels to OFX. Mutational analysis in gyrA and gyrB genes and genotype analysis of M. tuberculosis isolates was done by gene-specific polymerase chain reaction (PCR) followed by DNA sequencing and spoligotyping, respectively. Three (6.25%), 12 (44.44%) and 12 (29.27%) MDR-TB isolates from western, northern and southern India, respectively, were found to be OFX-resistant MDR-TB isolates. OFX resistance was observed to be significantly higher in MDR-TB cases for all study regions. Beijing genotypes from northern India were observed to be associated with OFX-resistant MDR-TB cases (P <0.05). Among 35 (30.15%) phenotypically OFX-resistant isolates, 22 (62.86%) had mutations in the gyrA gene and two (5.71%) isolates had mutations in the gyrB gene. These results caution against the PCR-based prediction of OFX resistance patterns and highlight the need for searching other genetic loci for the detection of mutations conferring resistance to OFX in M. tuberculosis. Our study also showed the usefulness of NRA as an alternative method to detect OFX resistance.
Sections du résumé
Background & objectives
Drug resistance surveillance offers useful information on trends of drug resistance and the efficacy of control measures. Studies and reports of drug-resistant mutations and phenotypic assays thus become important. This study was conducted to investigate the molecular characteristics of ofloxacin (OFX)-resistant, multidrug-resistant tuberculosis (MDR-TB) isolates from different geographical regions of India and their association with strains of different genotypes. Further, the nitrate reductase assay (NRA) was tested against Mycobacteria Growth Indicator Tube(MGIT) for the determination of OFX resistance as an alternative and cost-effective method.
Methods
A total of 116 Mycobacterium tuberculosis isolates were used to assess the mutations in the gyrA, gyrB genes and resistance levels to OFX. Mutational analysis in gyrA and gyrB genes and genotype analysis of M. tuberculosis isolates was done by gene-specific polymerase chain reaction (PCR) followed by DNA sequencing and spoligotyping, respectively.
Results
Three (6.25%), 12 (44.44%) and 12 (29.27%) MDR-TB isolates from western, northern and southern India, respectively, were found to be OFX-resistant MDR-TB isolates. OFX resistance was observed to be significantly higher in MDR-TB cases for all study regions. Beijing genotypes from northern India were observed to be associated with OFX-resistant MDR-TB cases (P <0.05). Among 35 (30.15%) phenotypically OFX-resistant isolates, 22 (62.86%) had mutations in the gyrA gene and two (5.71%) isolates had mutations in the gyrB gene.
Interpretation & conclusions
These results caution against the PCR-based prediction of OFX resistance patterns and highlight the need for searching other genetic loci for the detection of mutations conferring resistance to OFX in M. tuberculosis. Our study also showed the usefulness of NRA as an alternative method to detect OFX resistance.
Identifiants
pubmed: 32461400
pii: IndianJMedRes_2020_151_4_361_284218
doi: 10.4103/ijmr.IJMR_493_18
pmc: PMC7371067
doi:
Substances chimiques
Antitubercular Agents
0
Ofloxacin
A4P49JAZ9H
Peptide Hydrolases
EC 3.4.-
nitrate reductase inactivating enzyme
EC 3.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
361-370Déclaration de conflit d'intérêts
None
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