NorA, Tet(K), MepA, and MsrA Efflux Pumps in Staphylococcus aureus, their Inhibitors
and 1,8-Naphthyridine Sulfonamides

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; Teresinha   Gonçalves   da Silva
doi:10.2174/1381612829666221212101501
Abstract

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.
Keywords: 1, 8-naphthyridines, efflux pump inhibitors, NorA, Staphylococcus aureus, Tet(K), antibiotic resistance.
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DOI https://dx.doi.org/10.2174/1381612829666221212101501	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286
Current Pharmaceutical Design

NorA, Tet(K), MepA, and MsrA Efflux Pumps in Staphylococcus aureus, their Inhibitors and 1,8-Naphthyridine Sulfonamides

Abstract

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NorA, Tet(K), MepA, and MsrA Efflux Pumps in Staphylococcus aureus, their Inhibitors and 1,8-Naphthyridine Sulfonamides

Abstract

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