Genetic diversity among multidrug-resistant Mycobacterium tuberculosis strains in Mexico

Martínez-Guarneros, Armando; Rastogi, Nalin; Couvin, David; Escobar‐Gutiérrez, Alejandro; Rossi, Liana Chesini; Vazquez-Chacon, Carlos A.; Rivera-Gutierrez, Sandra; Lozano, Daniela; Vergara-Castañeda, Arely; González-y-Merchand, Jorge A.; Vaughan, Gilberto

doi:10.1016/j.meegid.2012.12.024

Cited by 33 publications

(36 citation statements)

References 22 publications

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“…The clusters SIT42 (LAM9) and SIT8 (EAI5) comprised three and seven strains, respectively, and were the only ones that showed some degree of clonality for EMB r isolates, but an embB 306 mutation was present in only one and two isolates, respectively. These data confirm preliminary information related to the high diversity and increasing presence of East-African Indian (EAI) and LatinAmerican Mediterranean (LAM) lineages circulating in Mexico and that are frequently associated with MDR-TB (36,37).…”

Section: Discussionsupporting

confidence: 82%

Mutation atembBCodon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

Cuevas-Córdoba

Juarez-Eusebio

Almaraz-Velasco

et al. 2015

Antimicrob Agents Chemother

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dEthambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMB r ), 49 were sensitive to ethambutol (EMB s ) but were resistant to another drug, and 65 were pansensitive isolates (P s ). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the P s isolates ( The mismanagement of patients and inadequate administration of antimicrobial therapy are the most important factors contributing to the development of drug-resistant TB (DR-TB). According to the WHO, DR-TB has become a major public health problem in several settings and, depending on the particular country, 5% of TB new cases and 20% of previously treated cases exhibit simultaneous resistance to isoniazid (INH) and rifampin (RIF) and an aggravated form of DR-TB known as multidrugresistant TB (MDR-TB) (2).Ethambutol (EMB) was introduced in 1961 as a bacteriostatic agent effective against actively growing mycobacteria. It is currently used in combination with other first-line drugs, such as INH and RIF, for the treatment of new TB cases and, depending on the resistance profile, retreatment cases (3). Resistance to EMB has been associated with acquired mutations in the emb cluster of three contiguous genes named embC, embA, and embB (4, 5). The embA and embB genes encode arabinosyl transferases involved in the arabinosylation of arabinogalactan, while embC is implicated in the arabinosylation of lipoarabinomannan (6-8).Several studies have identified mutations at codon 306 of embB as the most common alterations in EMB-resistant (EMB r ) isolates (9-20). However, the occurrence of embB codon 306 mutations in EMB-susceptible isolates (EMB s ) and the absence of mutations in EMB r isolates have raised questions regarding the utility of this codon as a potential marker for resistance (11,19,(21)(22)(23)(24). In addition, a significant increase in the proportion of MDR-TB strains bearing embB 306 mutations has recently been observed (25, 26), and 10 mutations from codons 306 to 508 of embB have been suggested as candidate markers for the prediction of quadruple resistance to INH, RIF, streptomycin (STR), and EMB (27). The identification of mu...

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Section: Discussionsupporting

confidence: 82%

Mutation atembBCodon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

Cuevas-Córdoba

Juarez-Eusebio

Almaraz-Velasco

et al. 2015

Antimicrob Agents Chemother

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“…In the patient population examined in this study, eight lineages were found, with the X, LAM, T and H lineages accounting for 68% of the isolates. All of these lineages have been previously described in Mexico; however, direct comparison with other lineage reports reveals an unusually high frequency of lineages X and LAM (Molina Torres et al 2010, Nava-Aguilera et al 2011, Zenteno-Cuevas et al 2012, Martínez-Guarneros et al 2013). …”

Section: Discussionmentioning

confidence: 69%

“…Reports from Mexico describe a significant variation of isolates with Indo-Oceanic and Asian lineages, according to geographic region. In northern states, the Indo-Oceanic and Asian lineages are scarce or absent, despite the strong human migration patterns that exist with proximity to the USA (Molina-Torres et al 2010, Martínez-Guarneros et al 2013). In central and southeastern Mexico, occurrences of less than 3% are observed for these lineages (Martínez-Gamboa et al 2008, Zenteno-Cuevas et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis from Mexico

Zenteno-Cuevas

Silva-Hernández

Mendoza-Damián

et al. 2013

Mem. Inst. Oswaldo Cruz

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Tuberculosis (TB) is an infectocontagious respiratory disease caused by members of the Mycobacterium tuberculosis complex. A 7 base pair (bp) deletion in the locus polyketide synthase (pks)15/1 is described as polymorphic among members of the M. tuberculosis complex, enabling the identification of Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to characterise this locus in TB isolates from Mexico. One hundred twenty clinical isolates were recovered from the states of Veracruz and Estado de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the locus pks15/1, while genotypic characterisation was performed by spoligotyping. One hundred and fifty isolates contained the 7 bp deletion, while five had the wild type locus. Lineages X (22%), LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates were identified as Beijing and two (1%) EAI-Manila. The wild type pks15/1 locus was observed in all Asian lineage isolates tested. Our results confirm the utility of locus pks15/1 as a molecular marker for identifying Asian lineages of the M. tuberculosis complex. This marker could be of great value in the epidemiological surveillance of TB, especially in countries like Mexico, where the prevalence of such lineages is unknown.

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“…All strains were typed by spoligotyping [9] and 24-loci MIRUVNTRs [27,28] as described earlier [29]. Spoligotypes in binary format were converted to an octal code for comparison with SIT-VIT2 proprietary database of Institut Pasteur de la Guadeloupe, which is an updated version of SITVITWEB [30], available online at http://www.pasteur-guadeloupe.fr:8081/SITVIT_ONLINE.…”

Section: Genotyping and Database Comparisonmentioning

confidence: 99%

Human multidrug-resistant Mycobacterium bovis infection in Mexico

et al. 2015

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Genetic diversity among multidrug-resistant Mycobacterium tuberculosis strains in Mexico

Cited by 33 publications

References 22 publications

Mutation atembBCodon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

Mutation atembBCodon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis from Mexico

Human multidrug-resistant Mycobacterium bovis infection in Mexico

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