Felise G Adams, Saleh Alquethamy, Jack K Waters, Brynley J Davies, Ella Haracic, Jeffrey D Nanson, James C Paton, Jade K Forwood, Karl A Hassan, Erin B Brazel, Claudia Trappetti, Bart A Eijkelkamp
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引用次数: 0
Abstract
Acinetobacter baumannii is a hospital-associated pathogen with unique fatty acid homeostasis features. This includes a reliance on desaturases for proliferation, due to an inability to generate unsaturated fatty acids during the synthesis cycles. However, there are various unexplained gaps in A. baumannii fatty acid homeostasis, such as the desaturation of de novo synthesized fatty acids. We identified a conserved desaturase (DesC) with a rare structural feature that may have roles in coordinating fatty acids with acyl carrier protein conjugants. We showed that DesC can generate fatty acids with cis double bonds in the delta-9 position. Profiling of A. baumannii fatty acids and mRNA transcripts emphasized its significance during fatty acid synthesis. DesC was found to be most critical in mouse niches where A. baumannii relies on fatty acid synthesis. This work has contributed to our understanding of core metabolic features that are key to the disease potential of A. baumannii.
期刊介绍:
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.