Cícera Datiane de Morais Oliveira-Tintino, Débora Feitosa Muniz, Cristina Rodrigues dos Santos Barbosa, Raimundo Luiz Silva Pereira, Iêda Maria Begnini, Ricardo Andrade Rebelo, Luiz Everson da Silva, Sandro Lucio Mireski, Michele Caroline Nasato, Maria Isabel Lacowicz Krautler, Carlos Vinicius Barros Oliveira, Pedro Silvino Pereira, Alexandre Magno Rodrigues Teixeira, Saulo Relison Tintino, Irwin Rose Alencar de Menezes, Henrique Douglas Melo Coutinho* and Teresinha Gonçalves da Silva Pages 323 - 355 ( 33 )
Antibiotic resistance can be characterized, in biochemical terms, as an antibiotic’s inability to reach its bacterial target at a concentration that was previously effective. Microbial resistance to different agents can be intrinsic or acquired. Intrinsic resistance occurs due to inherent functional or structural characteristics of the bacteria, such as antibiotic-inactivating enzymes, nonspecific efflux pumps, and permeability barriers. On the other hand, bacteria can acquire resistance mechanisms via horizontal gene transfer in mobile genetic elements such as plasmids. Acquired resistance mechanisms include another category of efflux pumps with more specific substrates, which are plasmid-encoded. Efflux pumps are considered one of the main mechanisms of bacterial resistance to antibiotics and biocides, presenting themselves as integral membrane transporters. They are essential in both bacterial physiology and defense and are responsible for exporting structurally diverse substrates, falling into the following main families: ATP-binding cassette (ABC), multidrug and toxic compound extrusion (MATE), major facilitator superfamily (MFS), small multidrug resistance (SMR) and resistance-nodulation-cell division (RND). The Efflux pumps NorA and Tet(K) of the MFS family, MepA of the MATE family, and MsrA of the ABC family are some examples of specific efflux pumps that act in the extrusion of antibiotics. In this review, we address bacterial efflux pump inhibitors (EPIs), including 1,8-naphthyridine sulfonamide derivatives, given the pre-existing knowledge about the chemical characteristics that favor their biological activity. The modification and emergence of resistance to new EPIs justify further research on this theme, aiming to develop efficient compounds for clinical use.
1,8-naphthyridines, efflux pump inhibitors, NorA, Staphylococcus aureus, Tet(K), antibiotic resistance.