Rojony Rajoana, Danelishvili Lia, Campeau Anaamika, Wozniak Jacob M, Gonzalez David J, Bermudez Luiz E
Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Department of Pharmacology, School of Medicine, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA 92093, USA.
Microorganisms. 2020 May 9;8(5):698. doi: 10.3390/microorganisms8050698.
subsp. (MAB) is a clinically important nontuberculous mycobacterium (NTM) causing pulmonary infection in patients such as cystic fibrosis and bronchiectasis. MAB is naturally resistant to the majority of available antibiotics. In attempts to identify the fundamental response of MAB to aerobic, anaerobic, and biofilm conditions (as it is encountered in patients) and during exposure to antibiotics, we studied bacterial proteome using tandem mass tag mass spectrometry sequencing. Numerous de novo synthesized proteins belonging to diverse metabolic pathways were found in anaerobic and biofilm conditions, including glycolysis/gluconeogenesis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, nitrogen metabolism, and glyoxylate and dicarboxylate metabolism. Upon exposure to amikacin and linezolid under stress environments, MAB displayed metabolic enrichment for glycerophospholipid metabolism and oxidative phosphorylation. By comparing proteomes of two significant NTMs, MAB and subsp. , we found highly synthesized shared enzymes of oxidative phosphorylation, TCA cycle, glycolysis/gluconeogenesis, glyoxylate/dicarboxylate, nitrogen metabolism, peptidoglycan biosynthesis, and glycerophospholipid/glycerolipid metabolism. The activation of peptidoglycan and fatty acid biosynthesis pathways indicates the attempt of bacteria to modify the cell wall, influencing the susceptibility to antibiotics. This study establishes global changes in the synthesis of enzymes promoting the metabolic shift and enhancing the pathogen resistance to antibiotics within different environments.
亚种（MAB）是一种临床上重要的非结核分枝杆菌（NTM），可在诸如囊性纤维化和支气管扩张症患者中引起肺部感染。MAB对大多数现有抗生素具有天然抗性。为了确定MAB在需氧、厌氧和生物膜条件下（如在患者体内所遇到的情况）以及在接触抗生素期间的基本反应，我们使用串联质量标签质谱测序研究了细菌蛋白质组。在厌氧和生物膜条件下发现了许多属于不同代谢途径的从头合成蛋白质，包括糖酵解/糖异生、三羧酸（TCA）循环、氧化磷酸化、氮代谢以及乙醛酸和二羧酸代谢。在应激环境下暴露于阿米卡星和利奈唑胺后，MAB在甘油磷脂代谢和氧化磷酸化方面表现出代谢富集。通过比较两种重要的非结核分枝杆菌MAB和亚种的蛋白质组，我们发现了氧化磷酸化、TCA循环、糖酵解/糖异生、乙醛酸/二羧酸、氮代谢、肽聚糖生物合成以及甘油磷脂/甘油脂代谢中高度合成的共享酶。肽聚糖和脂肪酸生物合成途径的激活表明细菌试图修饰细胞壁，从而影响对抗生素的敏感性。本研究确定了在不同环境中促进代谢转变并增强病原体对抗生素抗性的酶合成的全局变化。
