Deciphering the structure of a multi-drug resistant Acinetobacter baumannii short-chain dehydrogenase reductase.

Autor: Shahri MA; School of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia.; Menzies Health Institute Queensland and School of Medical Sciences, Griffith University, Gold Coast, QLD, Australia., Shirmast P; Menzies Health Institute Queensland and School of Medical Sciences, Griffith University, Gold Coast, QLD, Australia., Ghafoori SM; School of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia., Forwood JK; School of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Feb 23; Vol. 19 (2), pp. e0297751. Date of Electronic Publication: 2024 Feb 23 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0297751
Abstrakt: The rapidly increasing threat of multi-drug-resistant Acinetobacter baumannii infections globally, encompassing a range of clinical manifestations from skin and soft tissue infections to life-threatening conditions like meningitis and pneumonia, underscores an urgent need for novel therapeutic strategies. These infections, prevalent in both hospital and community settings, present a formidable challenge to the healthcare system due to the bacterium's widespread nature and dwindling effective treatment options. Against this backdrop, the exploration of bacterial short-chain dehydrogenase reductases (SDRs) emerges as a promising avenue. These enzymes play pivotal roles in various critical bacterial processes, including fatty acid synthesis, homeostasis, metabolism, and contributing to drug resistance mechanisms. In this study, we present the first examination of the X-ray crystallographic structure of an uncharacterized SDR enzyme from A. baumannii. The tertiary structure of this SDR is distinguished by a central parallel β-sheet, consisting of seven strands, which is flanked by eight α-helices. This configuration exhibits structural parallels with other enzymes in the SDR family, underscoring a conserved architectural theme within this enzyme class. Despite the current ambiguity regarding the enzyme's natural substrate, the importance of many SDR enzymes as targets in anti-bacterial agent design is well-established. Therefore, the detailed structural insights provided in this study open new pathways for the in-silico design of therapeutic agents. By offering a structural blueprint, our findings may provide a platform for future research aimed at developing targeted treatments against this and other multi-drug-resistant infections.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Shahri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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