2015
DOI: 10.1128/aac.00150-15
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Molecular Analysis of the embCAB Locus and embR Gene Involved in Ethambutol Resistance in Clinical Isolates of Mycobacterium tuberculosis in France

Abstract: Modification of codon 306 in embB is regarded as the main mechanism leading to ethambutol (ETB) resistance in clinical isolates of Mycobacterium tuberculosis. However, numerous mutations elsewhere in the embCAB locus and in embR, a putative transcriptional activator of this locus, have been reported to be involved in ETB resistance. Here, we investigated the diversity of nucleotide variations observed in embCAB and embR in M. tuberculosis complex isolates from France. These regions were sequenced in 71 ETB-res… Show more

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Cited by 55 publications
(45 citation statements)
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References 49 publications
(99 reference statements)
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“…Moreover, 75.0% of the mutations found in EMB-susceptible embB306 mutants occurred in MDR isolates, and the remaining 25.0% occurred in INH-or RIF-resistant isolates. In total, 56.5% of the EMB-resistant isolates enrolled in this study harbored embB306 mutations, a value that is consistent with previous data from Spain (53.7%) (17), France (56%) (18), and a comprehensive study of isolates from Australia, Colombia, India, Mexico, New York City, Spain, and Texas (50%) (7) but higher than the values reported from South Korea (47.6%) (19), northwestern Russia (48.3%) (15), and Mexico (33%) (20) and lower than the values reported from Germany (68%) (5) and Singapore (68%) (21). A strong correlation between embB306 mutations and resistance to EMB, INH, and RIF and MDR was found, indicating that embB306 mutations are associated with broad antibiotic resistance rather than simply EMB resistance.…”
Section: Discussionsupporting
confidence: 80%
“…Moreover, 75.0% of the mutations found in EMB-susceptible embB306 mutants occurred in MDR isolates, and the remaining 25.0% occurred in INH-or RIF-resistant isolates. In total, 56.5% of the EMB-resistant isolates enrolled in this study harbored embB306 mutations, a value that is consistent with previous data from Spain (53.7%) (17), France (56%) (18), and a comprehensive study of isolates from Australia, Colombia, India, Mexico, New York City, Spain, and Texas (50%) (7) but higher than the values reported from South Korea (47.6%) (19), northwestern Russia (48.3%) (15), and Mexico (33%) (20) and lower than the values reported from Germany (68%) (5) and Singapore (68%) (21). A strong correlation between embB306 mutations and resistance to EMB, INH, and RIF and MDR was found, indicating that embB306 mutations are associated with broad antibiotic resistance rather than simply EMB resistance.…”
Section: Discussionsupporting
confidence: 80%
“…Therefore, ethambutol resistance was not considered in the present study. However, we showed recently that adding the search for mutations at codon 406 or 497 in embB and for mutations in the embCembA intergenic region to the search for mutations at codon 306 in embB could dramatically increase the sensitivity of the test (18).…”
Section: Discussionmentioning
confidence: 99%
“…Many specific mutations associated with drug resistance have been described (7)(8)(9)(10), and molecular assays targeting these mutations have improved the turnaround time (TAT) to detect resistance (11)(12)(13). However, these assays are limited to interrogating small portions of the genome (14), and strains of M. tuberculosis acquire resistance to drugs through various mechanisms, including chromosomal insertions, deletions, and single-nucleotide polymorphisms (SNPs). Transmissible mobile genetic elements, such as plasmids and transposons, do not play a significant role in M. tuberculosis drug resistance (15,16).…”
mentioning
confidence: 99%