Although the encountered mutations in resistant samples were not observed in susceptible isolates, their association with SM-resistance needs to be confirmed. Three contiguous genes encoding arabinosyl transferases and designated embC, embA, and embB were analyzed in the present study. These 3 genes have been identified in M. tuberculosis[52]. Previous studies based find more on limited sequencing region containing the embCAB genes have identified mutations that result in replacement of amino acid residues and are
found only in EMB-resistant organisms cultured from humans [52]. In this study, the embB analysis gene identified 1 of 2 resistant isolates with EMB-resistance-associated nucleotide substitutions in codon 306ATG → GTG that result in amino acid replacement (Met → Val). This is in accordance with others studies analyzing EMB-resistant clinical isolates of M. tuberculosis that identified embB amino acid-conferring mutations in approximately 50 to 70% isolates with resistance-associated polymorphisms [52]. Certain PARP inhibitor cancer variations affecting embA (330CTG → TTG) and embC (-20A → C and -230 A → C) appeared to be not associated with drug resistance.
Given the low number of EMB-resistant isolates in our investigation further studies are needed to confirm these findings. Selleckchem QVDOph Conclusion This study provided the first molecular characterization of M. tuberculosis drug resistance in the Central Region of Cameroon using DNA sequencing. rpoB and katG315 mutations known to be involved in resistance had high specificities and sensitivities for detecting RIF- and INH-resistance respectively. However, the correlation between molecular Dehydratase and phenotypic resistance testing for the determination of SM- and EMB-resistance was lower. This study clearly shows the need for continuous phenotypic and genotypic characterization of drug resistance
at the national level in order to determine the most suitable molecular marker for drug resistance in our setting. The fact that mutations at codon katG315 and at the rpoB gene show high specificities for resistance against INH or RIF respectively suggests that these may be suitable molecular marker for diagnostic test in Cameroon. Consequently the WHO recommended GeneXpert technology is appropriate for the detection RIF-resistance in the Central Region of Cameroon. Acknowledgements This study was financially supported by CANTAM EDCTP grant N° CB.2007.41700.006. Emmanuel Mouafo Tekwu and Larissa Kamgue Sidze were research fellow students at the Institute for Tropical Medicine in Tübingen (Germany). Veronique Penlap Beng, Francine Ntoumi, Emmanuel Mouafo Tekwu, Larissa Kamgue Sidze, Jean-Paul Assam Assam and Matthias Frank were supported by the DAAD PAGEL-Program of the University of Tübingen to attend expert meetings and workhops throughout the duration of the project.