Reducing bacterial antibiotic resistance by targeting bacterial metabolic pathways and disrupting RND efflux pump activity

Abstract

Antibiotic resistance is a significant issue for the medical community, worldwide. Many bacteria develop drug resistance by utilizing multidrug resistant or MDR efflux pumps that can export antibiotics from bacterial cells. Antibiotics are expelled from bacteria by efflux pumps a part of the resistance nodulation division (RND) family. Types of RND efflux pumps include the AcrAB-TolC tripartite protein pump. There are an excessive number of antibiotic compounds that have been discovered; however, only a few antibiotics are effective against MDR bacteria. Many bacteria become drug resistant when sharing genes that encode MDR efflux pump expression. MDR efflux pump encoding genes are incorporated into plasmids and then shared among bacteria. As a consequence, advancements in genetic engineering can sufficiently target and edit pathogenic bacterial genomes for perturbing drug resistance mechanisms. In this perspective and review, support will be provided for utilizing genetic modifications as an antimicrobial approach and tool that may effectively combat bacterial MDR. Ayhan et al. found that deleting acrB, acrA, and tolC increased the levels of antibiotic sensitivity in Escherichia coli. Researchers also found that glucose, glutamate, and fructose all induced the absorption of antibiotics by upregulating the gene expression of maeA and maeB that is a part of the MAL-pyruvate pathway. Therefore, the current perspective and review will discuss the potential efficacy of reducing antibiotic resistance by inhibiting genes that encode efflux protein pump expression while simultaneously upregulating metabolic genes for increased antibiotic uptake.

Antibacterial Activity and Mechanism of Madecassic Acid against Staphylococcus aureus

“…The antibacterial mechanism of MA is from our research, as shown in Figure 15 . As antibiotic resistance has become the global challenge threating people’s health, and many pathogenic bacteria export antibiotics from intracellular environment through developing their multidrug efflux pumps system, which can be induced or evolved under long term excessive drug stress by modifying or regulating relative genes in plasmids [ 30 ], it is very urgent to develop new drugs or adjuvants to overcome antibiotic resistance. In this study, the multi-mechanical actions against S. aureus by MA were systemically verified, indicating that MA is a promising natural compound for controlling S. aureus infection.…”

Efflux Pumps as a Pharmacological Target to Combat Antibiotic Resistance

“…на гени, які регулюють метаболізм бактерій і генерують активність ефлюксної помпи, може змінити стійкість до антибіотиків [26]. Ці підходи дають можливість створювати інноваційні агенти, які можуть вибірково та ефективно блокувати ефлюксний насос [14].…”

Synthesis, Antibacterial, and Antioxidant Activities of Thiazolyl-Pyrazoline Schiff Base Hybrids: A Combined Experimental and Computational Study

“…In Silico Molecular Docking Simulation. Studies of docking simulations were carried out to identify the binding pattern of the synthesized compounds (16)(17)(18)(19)(20)(21)(22)(23)(24) to selected protein target active sites (i.e., DNA gyrase B, PqsA, pyruvate kinase, LuxS, and human peroxiredoxin 5) [56]. e binding affinity, hydrogen bond, and amino acid residual interactions (hydrophobic/π-cation/π-anion/π-alkyl and van der Waals interactions) of ligands (16)(17)(18)(19)(20)(21)(22)(23)(24) and standards are presented (SI Tables 7-11).…”