Abstract
Carvotacetones (1–7) isolated from Sphaeranthus africanus were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains Mycobacterium smegmatis mc2 155, Mycobacterium aurum ATCC 23366, and Mycobacterium bovis BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds 1 and 6 to accumulate ethidium bromide (EtBr) in M. smegmatis and M. aurum, a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds 1 and 6 were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against M. smegmatis. Carvotacetones 1 and 6 had potent antibacterial effects on M. aurum and M. bovis BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against M. smegmatis. Compound 1 appeared as the most efficient agent for impairing the efflux mechanism in M. smegmatis. Both compounds 1 and 6 were highly effective against M. aurum and M. bovis BCG. In particular, compound 1 was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections.
Highlights
Antimicrobial resistance (AMR) has developed against almost every known antibiotic [1]
Activity africanus were investigated for their antimicrobial
Sphaeranthus africanus wereinhibitory investigated for their antimicrobial
Summary
Antimicrobial resistance (AMR) has developed against almost every known antibiotic [1]. Due to the alarming spread of bacterial resistance worldwide, therapeutic treatment options for infectious diseases, such as tuberculosis (TB), are becoming more and more limited [4,5]. According to a recent report from the WHO, TB remains one of the top ten causes of death worldwide and the leading cause from a single infectious agent [6]. Among the numerous self-defense strategies of bacteria in order to resist the toxic action of antibiotics, efflux pumps are one of the key tools for facilitating bacterial survival [7]. Efflux pumps are membrane transport proteins found in both Gram-positive and -negative bacteria, as well as in eukaryotes. By extruding noxious compounds out of the cells, efflux pumps reduce the intracellular concentration of antibiotics [8]
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