Abstract
Variants of the microorganism Staphylococcus aureus which are resistant to antimicrobial agents exist as causative agents of serious infectious disease and constitute a considerable public health concern. One of the main antimicrobial resistance mechanisms harbored by S. aureus pathogens is exemplified by integral membrane transport systems that actively remove antimicrobial agents from bacteria where the cytoplasmic drug targets reside, thus allowing the bacteria to survive and grow. An important class of solute transporter proteins, called the major facilitator superfamily, includes related and homologous passive and secondary active transport systems, many of which are antimicrobial efflux pumps. Transporters of the major facilitator superfamily, which confer antimicrobial efflux and bacterial resistance in S. aureus, are good targets for development of resistance-modifying agents, such as efflux pump inhibition. Such modulatory action upon these antimicrobial efflux systems of the major facilitator superfamily in S. aureus may circumvent resistance and restore the clinical efficacy of therapy towards S. aureus infection.
Highlights
Bacteria are capable of overcoming the accumulation of drugs by transporting them to the outer membrane by a mechanism of active efflux which is mediated by drug efflux pumps
One of the main antimicrobial resistance mechanisms harbored by S. aureus pathogens is exemplified by integral membrane transport systems that actively remove antimicrobial agents from bacteria where the cytoplasmic drug targets reside, allowing the bacteria to survive and grow
Bacterial secondary active transporters involved in antimicrobial drug mechanisms are grouped under four families based on their sequence and functional similarities, namely: (i) Major facilitator super family (MFS); (ii) Resistance-nodulation-cell division transporter super family (RND); (iii) Small multidrug resistant transporter family (SMR); (iv) Multiple antimicrobial extrusion protein family (MATE)
Summary
Bacteria are capable of overcoming the accumulation of drugs by transporting them to the outer membrane by a mechanism of active efflux which is mediated by drug efflux pumps These drug efflux pumps can be grouped into primary and secondary active transporters. The secondary active transporters encompass those membrane proteins that use energy from a concentration gradient formerly established by a primary active transport process to transport a solute across the cellular membrane [3] They indirectly use the energy derived from ATP hydrolysis and transport molecules across an electrochemical concentration gradient by coupling with another compound [4]. Bacterial secondary active transporters involved in antimicrobial drug mechanisms are grouped under four families based on their sequence and functional similarities, namely:. Gene knockout and comparative transcriptome analysis of mutant versus the wild type can help to identify the functions of efflux pumps and their essential nature to the host bacterium
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