Acinetobacter baumannii Employs a Rare Fatty Acid Desaturase for Niche-Specific Host Adaptation

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
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 and 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.

Abstract Image

鲍曼不动杆菌利用一种罕见的脂肪酸去饱和酶进行生态位特异性宿主适应
鲍曼不动杆菌是一种与医院相关的病原体,具有独特的脂肪酸稳态特征。这包括依赖去饱和酶进行增殖,因为在合成周期中不能产生不饱和脂肪酸。然而,鲍曼不动杆菌脂肪酸稳态中存在各种无法解释的空白,例如新合成脂肪酸的去饱和。我们发现了一种保守的去饱和酶(DesC),它具有一种罕见的结构特征,可能在脂肪酸与酰基载体蛋白缀合物的协调中起作用。我们发现DesC可以在δ -9位置生成顺式双键的脂肪酸。鲍曼不动杆菌脂肪酸和mRNA转录物的分析强调了其在脂肪酸合成中的重要性。在鲍曼不动杆菌依赖脂肪酸合成的小鼠生态位中,DesC被发现是最关键的。这项工作有助于我们了解鲍曼不动杆菌的核心代谢特征,这些特征是致病潜力的关键。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
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.
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