In the regions where bedaquiline (BDQ) is introduced into the regimen, analysis of MIC and screening for preexisting resistance mutations could be crucial. The high prevalence of isolates with high BDQ MICs without prior exposure to BDQ was worrisome. It was also concluded that efflux pumps play a pivotal role in intrinsic BDQ resistance; therefore, the potential of verapamil as an adjunctive therapy to combat BDQ resistance should be investigated.

Background In order to shorten the course of treatment and its effectiveness, it is essential to gain an in-depth insight into the drug resistance mechanisms of Mycobacterium tuberculosis ( M. tuberculosis ). Methods In this study, we evaluated the contribution of 26 drug efflux pumps plus target gene mutations to the drug resistance levels in multi-drug resistant (MDR)/pre-extensively drug-resistant (pre-XDR)/extensively drug-resistant (XDR) and mono-drug resistant clinical isolates of M. tuberculosis . The panels of 25 M. tuberculosis clinical strains were characterized for drug resistance-associated mutations with whole-genome sequencing and antibiotic profiles in the presence and absence of efflux inhibitor verapamil (VP). Results Different MICs were observed for the same target gene mutations. Out of the 16 MDR/pre-XDR/XDR isolates, 6 (37.5%) and 3 (18.8%) isolates demonstrated a significant decrease in rifampicin (RIF) MIC and isoniazid (INH) MIC due to the VP exposure (64 μg/mL), respectively. Susceptibility to RIF was fully restored in two isolates after VP exposure. Moreover, the efflux pump genes of Rv2938, Rv2936, Rv1145, Rv1146, Rv933, Rv1250, Rv876 , Rv2333, Rv2459, Rv849, and Rv1819 were overexpressed in the presence of anti-TB drugs, showing the contribution of these efflux pumps to the overall resistance phenotype. Conclusions Our results clearly showed that efflux systems, besides spontaneous mutations, play a role in the development of INH/RIF resistance. In addition, although VP was effective in reducing the expression of some efflux pumps, it was not very successful at the phenotypic level. Electronic supplementary material The online version of this article (10.1186/s13756-019-0516-4) contains supplementary material, which is available to authorized users.

The emergence and spread of multidrug resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains is a critical global health problem. Between 2014 and 2018, 606 MTBC strains were isolated from 13,892 suspected pulmonary tuberculosis (TB) patients in Tehran, Iran, including 16 (2.6%) MDR-TB cases. A combination of phenotypic and genotypic methods (whole-genome sequencing) was employed for the identification of additional drug resistances and strain-to-strain genetic distances as a marker for recent transmission events. MDR and extensively drug-resistant (XDR) TB cases were almost exclusively infected by lineage 2/Beijing strains (14/16, P < 0.001). We further showed that recent transmission and/or recent introduction of lineage 2/Beijing strains contribute to high XDR-TB rates among all MDR-TB cases and should be considered an emerging threat for TB control in Tehran. In addition, the extensive pre-existing drug resistance profiles of MDR/XDR strains will further challenge TB diagnostics in the region.

The genus contains more than 150 species. Non-tuberculosis mycobacteria (NTM) often cause extrapulmonary and pulmonary disease. Mycobacteria detection at species level is necessary and provides useful information on epidemiology and facilitates successful treatment of patients. This retrospective study aimed to determine the incidence of the NTM isolates and (Mtb) in clinical specimens collected from Iranian patients during February 2011-December 2013, by PCR-restriction fragment length polymorphism analysis (PRA) of the gene. We applied conventional biochemical test and-PRA identification assay to identify species of mycobacteria in specimens from patients suspected of having mycobacterial isolates. This method was a sensitive, specific and effective assay for detecting mycobacterial species and had a 100% sensitivity and specificity for Mtb and (MAC) species. Using PRA for 380 mycobacterial selected isolates, including 317 Mtb, four and of the 59 clinical isolates, the most commonly identified organism was (35.6%), followed by (16.9%), (16.9%), (5.1%), (5.1%), (5.1%), (3.4%), (3.4%), (3.4%), (3.4%) and (1.7%). PRA method, in comparison with classical methods, is rapid, useful and sensitive for the phylogenetic analysis and species detection of mycobacterial strains. is the most common cause of infection by NTM in patients with non-HIV and HIV which demonstrated a high outbreak and diversity of NTM strains in our laboratory.

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