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

Frontiers in Microbiology
Diana MachadoMiguel Viveiros

Abstract

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, ...Continue Reading

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Citations

Oct 10, 2019·Endocrine, Metabolic & Immune Disorders Drug Targets·Manaf AlMatarFatih Köksal
Jul 14, 2018·Nature Reviews. Microbiology·Dijun DuBen F Luisi
Jul 19, 2018·Frontiers in Microbiology·Diana MachadoMarco Pieroni
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Jan 9, 2019·Frontiers in Microbiology·Diana MachadoMiguel Viveiros
Nov 20, 2020·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·M A Abo-KadoumJianping Xie
Dec 22, 2020·Frontiers in Microbiology·Barbara De SienaMargherita Sacco
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Oct 13, 2021·FEMS Microbiology Reviews·Sille RemmMarkus A Seeger

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Methods Mentioned

BETA
PCR
genotyping

Software Mentioned

VNTR plus
Epicenter
SITVITWEB
MIRU

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