RESUMO
Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.
RESUMO
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.
RESUMO
The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts in synergy with antimicrobials and that a main bioactive component allyl sulfide inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum lowered the MICs of multiple antibacterials. We conclude that A. sativum and allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances antibacterial agents.
