Antimicrobial resistance mediated by efflux pumps in Staphylococcus aureus and reversal strategy using sesquiterpenes: a literature review

Staphylococcus aureus is classified as a major pathogen responsible for nosocomial infections, ranging from mild infections to more severe complications that can lead to death. This species possesses several resistance mechanisms, among which efflux pumps stand out, as they are responsible for expelling significant amounts of antibiotics from within the bacterial cell, thereby reducing their effectiveness. Various natural compounds, including extracts, essential oils, or isolated substances, have shown promise in inhibiting efflux pumps in S. aureus strains. Sesquiterpenes are widely distributed in the plant kingdom and, due to their pharmacological properties, have garnered strong interest within the scientific community. According to studies in the literature, isolated natural products may act on efflux pumps, helping to restore the effectiveness of certain antibiotics that are targeted by bacterial resistance mechanisms. The mechanisms of efflux pump inhibition in multidrug-resistant bacteria are not yet fully understood. However, it is assumed that the inhibitor binds to the pump and blocks its function either competitively or non-competitively with the substrate, or disrupts the energy source required for extrusion. In light of the biological activities exhibited by these compounds, the present study aimed to conduct a narrative review, reporting sesquiterpenes as potential efflux pump inhibitors, as well as the genetic components involved in the overexpression of these structures in S. aureus.