Authors:

Teagan Young

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About Paper:

Antibiotic resistance is an escalating global concern, driven by the rise of multidrug-resistant pathogens, demanding the discovery and development of new antibiotics. Although efforts to limit antibiotic use in clinical settings have shown some promising outcomes, eliminating established resistance remains challenging, and new resistant strains continue to emerge. As bacteria adapt and evolve to evade current treatments, there is an ongoing need for therapeutics that target previously unexploited bacterial mechanisms. The Sodium-Dependent NADH: Ubiquinone Oxidoreductase (NQR) enzyme is a six-subunit respiratory enzyme complex found in several pathogenic bacteria, including V. cholerae, Pseudomonas, and Klebsiella species. While NQR performs a role in bacterial respiration similar to that of mitochondrial complex |, it is unique in terms of structure, mechanism, and phylogeny. NQR contributes to essential bacterial processes such as energy generation, motility, and toxin secretion. Our lab is focused on identifying potent inhibitors of NQR to serve as potential new antibiotics. A targeted library of ubiquinone-like compounds were screened against NQR, which identified a series of quinoline-based lead molecules that inhibit NQR activity and induce bacterial cell death. The synthesis and optimization of the ubiquinone-like lead compounds is progressing with a focus on enhancing potency and selectivity towards the NQR enzyme complex.

Source:

Loyola University Chicago

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Co-authors:

Teagan Young