Abstract
Mutations in target genes have been described in Mycobacterium tuberculosis Complex (MTBc) drug resistant isolates worldwide. In Mexico, not enough information has been reported in this concern. The aim of this study was to characterize mutations related to resistance to first line drugs in MTBc isolates from Oaxaca, Mexico. MTBc isolates were identified in clinical samples from Tuberculosis (TB) patients. Susceptibility to isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide was tested through nitrate reductase assay. PCR based analysis and sequencing were employed to characterize mutations in katG, inhA, rpoB, embB, rrs, rpsL and pncA genes. Mutations in katG and the promoter of the mabA-inhA operon were found in isoniazid resistant isolates. Sequence analysis of Rifampin Resistance-Determining Region in the rpoB gene showed novel mutations along this region besides mutations at codons 516, 526 and 531. Polymorphisms at codon 306 embB gene were found in ethambutol resistant isolates. Frequent mutations associated to resistance to streptomycin were characterized in rrs and/or rpsL genes. pncA analysis showed variable number of mutations in resistant and susceptible pyrazinamide isolates. Most frequent mutations related to resistance to first line antituberculous drugs were identified in phenotypically resistant MTBc isolates. New mutations were characterized in rpoB, rrs and rpsL genes.
Highlights
According to World Health Organization (WHO) tuberculosis (TB) is one of the top ten causes of death and the leading cause from a single infectious agent, causing 1.2 million deaths around the world
Mycobacterium species identification showed that in most isolates (37/38) M. tuberculosis was the infective species while M. bovis was present in one isolate (56-ex)
Our findings highlight that even punctual mutations have been useful in molecular diagnostic techniques to determine Drug Resistance (DR), it is time to analyze longer fragments of target genes as new DR mutations are being reported continuously. This is the first report about phenotypic drug resistance and molecular data in Mycobacterium tuberculosis Complex (MTBc) isolates from Oaxaca, Mexico, a region with scarce TB information
Summary
According to World Health Organization (WHO) tuberculosis (TB) is one of the top ten causes of death and the leading cause from a single infectious agent, causing 1.2 million deaths around the world. Mexico ranks third in the Americas region, just below Brazil and Peru, with 23 cases per 100,000 persons (WHO, 2019). Once TB is diagnosed, first line antituberculous drugs are administered: isoniazid (INH), rifampin (RIF), ethambutol (EMB), streptomycin (STR) and pyrazinamide (PZA). Antimycobacterial drugs may inhibit cell wall synthesis (INH, EMB), interfere with DNA replication and protein synthesis (RIF, STR) or acidify cytoplasmic environment altering metabolic pathways (PZA) (Fig. 1) (Cuevas-Córdoba et al, 2013a; Malone et al, 2016). Increasing number of TB cases is partly due to the transmission of drug resistant strains
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