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Flavonoids as Novel Efflux Pump Inhibitors and Antimicrobials Against Both Environmental and Pathogenic Intracellular Mycobacterial Species.

Abstract

Therapeutic treatment options for opportunistic non-tuberculous mycobacterial (NTM) infection and/or serious mycobacterial infections such as tuberculosis (TB) and leprosy are limited due to the spread of antimicrobial resistance mechanism. Plant-derived natural compounds as prospective efflux pump inhibitors may present a promising adjunct to conventional chemotherapy by enhancing mycobacterial susceptibility to antibiotics. This study served to evaluate the antimicrobial and resistance-modifying profile of a range of plant-derived flavonoids against the mycobacterial model strains: , , and BCG. The minimum inhibitory concentrations (MICs) of the compounds against the mycobacterial strains were determined using both agar dilution and broth dilution assays, while their efflux inhibitory activity was investigated via an ethidium bromide-based fluorometric assay. All compounds were screened for their synergistic effects with ethidium bromide (EtBr) and rifampicin (RIF) against . Skullcapflavone II (5,2'-dihydroxy-6,7,8,6'-tetramethoxyflavone, ) exerted potent antimicrobial activity against and BCG and considerably increased the susceptibility of to EtBr and RIF. Nobiletin (5,6,7,8,3',4'-hexamethoxyflavone, ) was determined to be the most potent efflux-inhibitor in and . However, a connection between strong modulatory and putative efflux activity of the compounds could not be observed. Nevertheless, the results highlight two polymethoxyflavones, skullcapflavone II and nobiletin, with potent antimycobacterial and antibiotic resistance modulating activities as valuable adjuvants in anti-mycobacterial therapies.

More information

Type
Journal Article
Author
Solnier J
Martin L
Bhakta S
Bucar F
Year of Publication
2020
Journal
Molecules (Basel, Switzerland)
Volume
25
Issue
3
Date Published
02/2020
Language
eng
ISSN Number
1420-3049
DOI
10.3390/molecules25030734
Alternate Journal
Molecules
PMID
32046221
Publication Language
eng