Kadja Luana Chagas Monteiro
◽
Thiago Mendonça de Aquino
◽
Francisco Jaime B. Mendonça Junior
Background:
Methicillin-resistant and vancomycin-resistant Staphylococcus aureus are
pathogens causing severe infectious diseases that pose real public health threats problems worldwide. In
S. aureus, the most efficient multidrug-resistant system is the NorA efflux pump. For this reason, it is
critical to identify efflux pump inhibitors.
Objective:
In this paper, we present an update of the new natural and synthetic compounds that act as
modulators of antibiotic resistance through the inhibition of the S. aureus NorA efflux pump.
Results:
Several classes of compounds capable of restoring the antibiotic activity have been identified
against resistant-S. aureus strains, acting as NorA efflux pump inhibitors. The most promising classes of
compounds were quinolines, indoles, pyridines, phenols, and sulfur-containing heterocycles. However,
the substantial degree structural diversity of these compounds makes it difficult to establish good structure-
activity correlations that allow the design of compounds with more promising activities and properties.
Conclusion:
Despite substantial efforts put forth in the search for new antibiotic adjuvants that act as
efflux pump inhibitors, and despite several promising results, there are currently no efflux pump inhibitors
authorized for human or veterinary use, or in clinical trials. Unfortunately, it appears that infection
control strategies have remained the same since the discovery of penicillin, and that most efforts remain
focused on discovering new classes of antibiotics, rather than trying to prolong the life of available antibiotics,
and simultaneously fighting mechanisms of bacterial resistance.
Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus
