Abstract
BackgroundThere is urgent need to discover new antimicrobial compounds with diverse chemical structures and mechanisms of action due to increasing new and re-emerging infectious diseases. Additionally, appearance of undesirable side effects of certain antibiotics and increasing resistance to antibiotics in current clinical use is also a cause for concern. Bacterial cell membranes are a possible target for developing new antibacterial drugs since membrane-based efflux pump systems play an important role in bacterial pathogenicity and antimicrobial resistance in bacteria. Hence, the objective of our study was to evaluate bacterial membrane integrity of two species of bacteria; Staphylococcus aureus and Pseudomonas aeruginosa, in the presence of ethanolic leaf extracts of two plant species Callistemon citrinus and Vernonia adoensis from Zimbabwe.MethodsBacterial efflux pump inhibition using both leaf extracts was determined by monitoring the transport of Rhodamine 6 G (R6G) across the cell membrane and IC50 values were obtained. Membrane permeabilizing properties of both extracts were also evaluated using the membrane potential sensitive dye 3’3 dipropylthiadicarbocyanine (diSC3-5). Haemolysis effect of both extracts on sheep erythrocytes was also investigated.ResultsBoth extracts inhibited bacterial efflux pumps which resulted in the accumulation of R6G inside the cell. The IC50 values for C. citrinus and V.adoensis against S. aureus were 1.44 mg/ml and 1.61 mg/ml, respectively. Both leaf extracts however, showed similar IC50 values of 1.64 mg/ml against P. aeruginosa. Both plant extracts showed some significant effects on permeability of the bacterial membrane when a 24-28% increase of diSC3-5 dye release was observed for S. aureus and 45–53% of dye was released from P. aeruginosa cell membrane after a 60 minute incubation period. In addition, both extracts exhibited haemolytic effects on sheep erythrocytes at concentrations greater than 2.5 mg/ml.ConclusionsThese plant extracts may provide new lead compounds for developing potential efflux pump inhibitors (EPIs) or permeabilising agents that could aid the transport of antibacterial agents into bacterial cells.
Highlights
There is urgent need to discover new antimicrobial compounds with diverse chemical structures and mechanisms of action due to increasing new and re-emerging infectious diseases
Efflux pumps reduce the accumulation of antibiotics inside of the bacterial cells, and the slow phase in which the process of antibiotic efflux takes place provides sufficient time for the bacterium to adapt to the antibiotics and become resistant through mutations or alteration of antibiotic targets [3]
Plant material C. citrinus was collected at the University of Zimbabwe campus in Harare province and V. adoensis was collected from Mashonaland Central (Centenary)
Summary
There is urgent need to discover new antimicrobial compounds with diverse chemical structures and mechanisms of action due to increasing new and re-emerging infectious diseases. Bacterial cell membranes are a possible target for developing new antibacterial drugs since membrane-based efflux pump systems play an important role in bacterial pathogenicity and antimicrobial resistance in bacteria. Throughout the world, about 50–75% of hospital deaths were reported due to infectious diseases [2]. These numbers continue to increase due to. Gram positive bacteria such as Staphylococcus aureus and Enterococcus faecalis represent an exponentially growing problem affecting communities worldwide [5]. Efflux pump-mediated resistance to single or multiple antimicrobial agents has raised serious concerns and has constricted the treatment options against bacterial infections. Due to the development of this resistance in human pathogens against commonly used antibiotics, it has become necessary to search for new antimicrobial substances from other sources including plants [6]
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