A systematic review of Mycobacterium leprae DNA gyrase mutations and their impact on fluoroquinolone resistance.

DNA Gyrase / genetics Drug Resistance, Bacterial / genetics Fluoroquinolones / pharmacology Humans Microbial Sensitivity Tests Mutation Mycobacterium leprae / enzymology
Fluoroquinolones GyrA GyrB Mutations Mycobacterium leprae Resistance Substitutions

Journal

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420

Informations de publication

Date de publication:
Nov 2021
Historique:
received: 19 01 2021
revised: 01 07 2021
accepted: 04 07 2021
pubmed: 16 7 2021
medline: 12 1 2022
entrez: 15 7 2021
Statut: ppublish

Résumé

The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance. This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB. Data source was PubMed. Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains. In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously. Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.

Sections du résumé

BACKGROUND BACKGROUND
The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance.
OBJECTIVES OBJECTIVE
This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB.
DATA SOURCES METHODS
Data source was PubMed.
STUDY ELIGIBILITY CRITERIA METHODS
Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains.
RESULTS RESULTS
In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously.
CONCLUSIONS CONCLUSIONS
Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.

Identifiants

DOI: 10.1016/j.cmi.2021.07.007 PMID: 34265461
pubmed: 34265461
pii: S1198-743X(21)00381-5
doi: 10.1016/j.cmi.2021.07.007
pii:
doi:

Substances chimiques

Fluoroquinolones 0
DNA Gyrase EC 5.99.1.3

Types de publication

Journal Article Review Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1601-1612

Informations de copyright

Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Auteurs

Aurélie Chauffour (A)

Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.

Florence Morel (F)

Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France; AP-HP, Sorbonne-Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France.

Florence Reibel (F)

Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France; AP-HP, Sorbonne-Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France; Laboratoire de Biologie, Groupe Hospitalier Nord-Essonne, Site de Longjumeau, Longjumeau, France.

Stéphanie Petrella (S)

Unité de Microbiologie Structurale, Institut Pasteur, CNRS UMR 3528, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Claudine Mayer (C)

Unité de Microbiologie Structurale, Institut Pasteur, CNRS UMR 3528, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Emmanuelle Cambau (E)

AP-HP GHU Nord, Service de Mycobactériologie Spécialisée et de Référence, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France; Université de Paris, Paris Diderot, INSERM, IAME UMR1137, Paris, France.

Alexandra Aubry (A)

Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France; AP-HP, Sorbonne-Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France. Electronic address: alexandra.aubry@sorbonne-universite.fr.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › DNA gyrase › A systematic review of Mycobacterium leprae...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance microbienne aux médicaments › Résistance bactérienne aux médicaments › A systematic review of Mycobacterium leprae...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › Quinolinone › Fluoroquinolones › A systematic review of Mycobacterium leprae...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A systematic review of Mycobacterium leprae...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité microbienne › A systematic review of Mycobacterium leprae...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › A systematic review of Mycobacterium leprae...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobacterium leprae › A systematic review of Mycobacterium leprae...