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

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.

Antibacterial Activity of the Essential Oil of Piper tuberculatum Jacq. Fruits against Multidrug-Resistant Strains: Inhibition of Efflux Pumps and β-Lactamase

“…It has experimentally been observed that the reduction in MIC efflux substrates such as antibiotics and EtBr indicates efflux pump inhibition by a test compound. Therefore, it is reasonable to assume that OEPT contains components that act as inhibitors of NorA, Tet(K), and MepA in S. aureus strains [ 56 , 57 ]. Additionally, the increased fluorescence emission by the strains indicates that the essential oil possibly inhibited the NorA and MepA efflux pumps.…”

Antimicrobial and Adjuvant Potencies of Di-n-alkyl Substituted Diazalariat Ethers

“…An important reason for the choice of S. aureus 1199B for study is that its resistance to norfloxacin is known to result from the presence of the Nor A efflux pump [50,68]. Efflux pumps require regulated ion balance to function so that exogeneous substances such as antibacterials can effectively be ejected.…”

Transcriptome Analysis of mfs2-Defective Penicillium digitatum Mutant to Reveal Importance of Pdmfs2 in Developing Fungal Prochloraz Resistance

“…isolates, P. digitatum strain HS-F6 and P. italicum strain YN1 [9,[26][27][28]. Unlike MFS and ABC, MATE superfamily transporters are usually associated with bacterial antibiotic resistance [29], and in contrast, contribute to fungal drug resistance in a few cases [30,31]. Genomics and RNA-seq studies revealed multiple iso-genes encoding MFS and ABC transporters as contributors to developing fungicide resistance.…”