Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran

Kardan-Yamchi, Jalil; Haeili, Mehri; Feyisa, Seifu Gizaw; Kazemian, Hossein; Shahraki, Abdolrazagh Hashemi; Zahednamazi, Fatemeh; Fooladi, Abbas Ali Imani; Feizabadi, Mohammad Mehdi

doi:10.1016/j.meegid.2015.08.036

Cited by 23 publications

(15 citation statements)

References 11 publications

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“…Rifampicin targets RNA polymerase β-subunit coded by rpoB gene, which has been found in all bacteria with different size and nucleotide sequence vary between bacterial species, including mycobacteria [44, 45]. The mutation in rpoB gene in MTB is the main cause for rifampicin resistance [10, 46, 47]. Previous studies reported that about 95% [10] of rifampicin resistance strains underwent mutation in the short region of the rpoB gene and currently an important target for screening this strain [10, 46].…”

Section: Discussionmentioning

confidence: 99%

Resistance of Mycobacterium tuberculosis strains to Rifampicin: A systematic review and meta-analysis

Feyisa

Abdurahman

Jimma

et al. 2019

Heliyon

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IntroductionAntitubercular drug resistance strain is a horrifying barrier to effective TB treatment and prevention. The present study aimed to determine the prevalence and geographical distribution of rifampicin-resistance M. tuberculosis (MTB) strains.MethodsWe searched two electronic databases, PubMed and EMBASE, until 26 March 2017 and updated our search on 27 April 2018 and accessed all prevalence studies of MTB strain and their drug susceptibility patterns to rifampicin. The pooled prevalence estimate was determined using random effects model.ResultsWe identified 23 studies satisfying the inclusion criteria. The proportion of rifampicin resistance strains was diverged depending on the type of strains, country and Regions. The pooled estimate of rifampicin-resistance strains of MTB for the included studies was 4% (95% CI: 3–5%). In subgroup analysis based on World Health Organization (WHO) Regions, the pooled estimate of rifampicin-resistance strains of MTB was 11% (95% CI: 9–13%) with the Western Pacific Region 24%, Europian Region 10%, South-East Asian Region 6%, African Region 3% and Region of American 1%. Beijing family was the most dominant strain resistance to rifampicin with pooled prevalence of 14% (95% CI: 10–18%). The pooled prevalence of other families, i.e. EAI, T, CAS, MANU, Haarlem, LAM and Ural, was ≤2% for each.ConclusionHigh burden of rifampicin resistance MTB strains was identified in the Western Pacific Region. Of these, Beijing family was predominantly resistance to rifampicin in Western Pacific Region and South-East Asian Region and also spread to European Region and Region of American.

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Section: Discussionmentioning

confidence: 99%

Resistance of Mycobacterium tuberculosis strains to Rifampicin: A systematic review and meta-analysis

Feyisa

Abdurahman

Jimma

et al. 2019

Heliyon

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“…Several recent studies have demonstrated the importance of the overexpression of efflux pump genes in MDR and XDR M . tuberculosis clinical strains (Calgin et al, 2013; Coelho et al, 2015; Li et al, 2015a; Yamchi et al, 2015; Kanji et al, 2016; Machado et al, 2016; Oh et al, 2017), in rifampicin monoresistant strains (Li et al, 2015b), or in the H37Rv susceptible strain after exposure to drugs (Garima et al, 2015; Caleffi-Ferracioli et al, 2016). Nevertheless, most of these studies are based on the simple assessment and evaluation of the levels of expression of M. tuberculosis efflux pump genes, and few have determined the effect of efflux inhibitors on the MICs of the antituberculosis drugs and have quantified the activity of the overexpressed efflux systems.…”

Section: Discussionmentioning

confidence: 99%

Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of Mycobacterium tuberculosis

et al. 2017

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Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and still is ignored by many. Here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resistance levels in clinical isolates of M. tuberculosis. A panel of 17 M. tuberculosis clinical strains were characterized for drug resistance associated mutations and antibiotic profiles in the presence and absence of efflux inhibitors. The correlation between the effect of the efflux inhibitors and the resistance levels was assessed by quantitative drug susceptibility testing. The bacterial growth/survival vs. growth inhibition was analyzed through the comparison between the time of growth in the presence and absence of an inhibitor. For the same mutation conferring antibiotic resistance, different MICs were observed and the different resistance levels found could be reduced by efflux inhibitors. Although susceptibility was not restored, the results demonstrate the existence of a broad-spectrum synergistic interaction between antibiotics and efflux inhibitors. The existence of efflux activity was confirmed by real-time fluorometry. Moreover, the efflux pump genes mmr, mmpL7, Rv1258c, p55, and efpA were shown to be overexpressed in the presence of antibiotics, demonstrating the contribution of these efflux pumps to the overall resistance phenotype of the M. tuberculosis clinical isolates studied, independently of the genotype of the strains. These results showed that the drug resistance levels of multi- and extensively-drug resistant M. tuberculosis clinical strains are a combination between drug efflux and the presence of target-gene mutations, a reality that is often disregarded by the tuberculosis specialists in favor of the almost undisputed importance of antibiotic target-gene mutations for the resistance in M. tuberculosis.

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“…Some efflux pumps have narrow substrate specificity (such as TetV pumps), but many transport a wide range of structurally dissimilar substrates and are known as MDR efflux pumps. The MFS family of MDR efflux pumps is found in many species of mycobacteria and includes several members that are relevant to antibiotic resistance (Yamchi et al, 2015). When overexpressed, MFS pumps confer clinically relevant levels of MDR and export an extremely wide range of substrates.…”

Section: Drug Resistance Mechanisms In Mycobacteriamentioning

confidence: 99%

“…For instance, studies that investigated the relevance of active efflux in the drug resistance of clinical strains of MTB indicated that jefA, drrA, drrB, efpA, mmr , and RV1217-Rv1218 efflux pumps were overexpressed under INH and RIF stress (Wang et al, 2013; Blair et al, 2015; Li et al, 2015). Furthermore, several studies indicated that some RIF or INH-resistant strains of MTB did not have sequence alterations in the core region of the drug target encoding genes (e.g., rpoB, katG, inhA ; Yamchi et al, 2015; Manson et al, 2017). Consequently, efflux pumps might play an important role in RIF- and INH- resistance in MTB, especially in those strains having no mutation in genes associated with INH and RIF resistance.…”

Section: Drug Resistance Mechanisms In Mycobacteriamentioning

confidence: 99%

New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria

et al. 2017

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Infectious diseases caused by clinically important Mycobacteria continue to be an important public health problem worldwide primarily due to emergence of drug resistance crisis. In recent years, the control of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (MTB), is hampered by the emergence of multidrug resistance (MDR), defined as resistance to at least isoniazid (INH) and rifampicin (RIF), two key drugs in the treatment of the disease. Despite the availability of curative anti-TB therapy, inappropriate and inadequate treatment has allowed MTB to acquire resistance to the most important anti-TB drugs. Likewise, for most mycobacteria other than MTB, the outcome of drug treatment is poor and is likely related to the high levels of antibiotic resistance. Thus, a better knowledge of the underlying mechanisms of drug resistance in mycobacteria could aid not only to select the best therapeutic options but also to develop novel drugs that can overwhelm the existing resistance mechanisms. In this article, we review the distinctive mechanisms of antibiotic resistance in mycobacteria.

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Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran

Cited by 23 publications

References 11 publications

Resistance of Mycobacterium tuberculosis strains to Rifampicin: A systematic review and meta-analysis

Resistance of Mycobacterium tuberculosis strains to Rifampicin: A systematic review and meta-analysis

Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of Mycobacterium tuberculosis

New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria

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