Abstract
The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use.
Highlights
Antimicrobial resistance (AMR) represents a public health concern worldwide and has been described as a “slow-moving tsunami” [1]
Targeting of bacterial efflux pumps via efflux pump inhibitors (EPIs) holds great promise as an approach to enhance the potency of existing antibiotic treatment regimens when co-administered
The results of the studies summarised in this review suggest that various new EPIs have been found in the last decade to have a potential to be utilised as adjuvants to antibiotic therapy against multidrug resistant (MDR) staphylococci
Summary
Antimicrobial resistance (AMR) represents a public health concern worldwide and has been described as a “slow-moving tsunami” [1]. There is a pressing need to identify alternative ways to safeguard the effectiveness of the currently used antimicrobials for the control of bacterial infections [22] One such orthogonal strategy complimentary to new antimicrobial discovery is the development of nonantimicrobial compounds, termed antibiotic adjuvants, that can diminish the emergence of resistance. The growing threat of efflux pump mediated AMR in staphylococci has driven research into identification of antimicrobial adjuvants This is required to safeguard the continued utility of anti-staphylococcal drugs and simultaneously decrease the selection of resistant mutants via multidrug efflux. Staphylococci are successful pathogens in establishing both acute and chronic infections in different human body sites due to their ability to efficiently regulate a wide arsenal of virulence factors and immune evasion mechanisms [31]
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