Bioactive compounds from the African medicinal plant Cleistochlamys kirkii as resistance modifiers in bacteria

Abstract

Cleistochlamys kirkii (Benth) Oliv. (Annonaceae) is a medicinal plant traditionally used in Mozambique to treat infectious diseases. The aim of this study was to find resistance modifiers in C. kirkii for Gram-positive and Gram-negative model bacterial strains. One of the most important resistance mechanisms in bacteria is the efflux pump-related multidrug resistance. Therefore, polycarpol (1), three C-benzylated flavanones (2-4), and acetylmelodorinol (5) were evaluated for their multidrug resistance-reverting activity on methicillin-susceptible and methicillin-resistant Staphylococcus aureus and Escherichia coli AG100 and AG100 A strains overexpressing and lacking the AcrAB-TolC efflux pump system. The combined effects of antibiotics and compounds (2 and 4) were also assessed by using the checkerboard microdilution method in both S. aureus strains. The relative gene expression of the efflux pump genes was determined by real-time reverse transcriptase quantitative polymerase chain reaction. The inhibition of quorum sensing was also investigated. The combined effect of the antibiotics and compound 2 or 4 on the methicillin-sensitive S. aureus resulted in synergism. The most active compounds 2 and 4 increased the expression of the efflux pump genes. These results suggested that C. kirkii constituents could be effective adjuvants in the antibiotic treatment of infections.

Nigella sativa essential oil and its bioactive compounds as resistance modifiers against Staphylococcus aureus

“…The MICs of N. sativa EO and its bioactive compounds were determined according to the Clinical and Laboratory Standard Institute guidelines in three independent assays (Kincses et al, ).…”

Recent updates of fluoroquinolones as antibacterial agents

“…Lactone represents an important antibacterial pharmacophore which can bind with tyrosyl‐tRNA synthetase . Hence, coupling of lactone derivatives with fluoroquinolones gave a series of novel multi‐target hybrids . This study indicated that fluoroquinolone moieties influenced the antibacterial activity greatly, and ciprofloxacin was optimal for activity .…”

“…Lactone represents an important antibacterial pharmacophore which can bind with tyrosyl‐tRNA synthetase . Hence, coupling of lactone derivatives with fluoroquinolones gave a series of novel multi‐target hybrids .…”

Standard operating procedure (SOP) for disk diffusion-based quorum sensing inhibition assays

“…Disk diffusion is a simple method for screening the susceptibility of various microorganisms against drugs/candidate molecules: it is user-friendly, and there is a lot of experience accumulated due to its use in routine clinical microbiology. Disk-diffusion based QS-inhibitory (DDBQSI) assay utilizing QS-signal molecule producing strains and signal molecule-reporter strains (e.g., Agrobacterium, Chromobacterium, Pseudomonas, Serratia and Vibrio species) is the most frequently used method [36][37][38][39][40]. The advantage of this method is its simple execution, the highthroughput nature and its usability in resourcescarce settings [41].…”