Metabolic Mechanism and Physiological Role of Glycerol 3-Phosphate in Pseudomonas aeruginosa PAO1.
Metabolic Mechanism and Physiological Role of Glycerol 3-Phosphate in Pseudomonas aeruginosa PAO1.
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作者：
铜绿假单胞菌是囊性纤维化患者致死的重要条件致病菌。铜绿假单胞菌可以利用CF患者肺表面主要活性物质磷脂酰胆碱降解产生的甘油。先前的研究表明，这种细菌对甘油的代谢有助于其对CF肺环境的适应和持久性。在这里，我们研究了甘油及其重要的代谢中间体3-磷酸甘油(G3P)在铜绿假单胞菌PAO1中的代谢机制。我们发现G3P动态平衡在铜绿假单胞菌PAO1的生长和毒力因子的产生中起着重要作用。由G3P脱氢酶(GlpD)突变和外源甘油引起的G3P积累导致生长受阻，导致绿青素合成、运动能力、对氧化胁迫的耐受性和对卡那霉素的抗药性下降。转录分析表明，G3P胁迫导致的生长迟缓与糖酵解和三磷酸腺苷(ATP)合成减少有关。此外，还鉴定了在菌株PAO1中对G3P的脱磷起作用的两种卤酸脱卤酶样磷酸酶(PA0562和PA3172)，并对它们的酶学性质进行了研究。我们的发现揭示了G3P动态平衡的重要性，并表明G3P分解代谢的关键酶GlpD是预防和治疗该病原体感染的潜在治疗靶点。
Pseudomonas aeruginosa is an important opportunistic pathogen that is lethal to cystic fibrosis (CF) patients. Glycerol generated during the degradation of phosphatidylcholine, the major lung surfactant in CF patients, could be utilized by P. aeruginosa. Previous studies have indicated that metabolism of glycerol by this bacterium contributes to its adaptation to and persistence in the CF lung environment. Here, we investigated the metabolic mechanisms of glycerol and its important metabolic intermediate glycerol 3-phosphate (G3P) in P. aeruginosa PAO1. We found that G3P homeostasis plays an important role in the growth and virulence factor production of P. aeruginosa PAO1. The G3P accumulation caused by the mutation of G3P dehydrogenase (GlpD) and exogenous glycerol led to impaired growth and reductions in pyocyanin synthesis, motilities, tolerance to oxidative stress, and resistance to kanamycin. Transcriptomic analysis indicates that the growth retardation caused by G3P stress is associated with reduced glycolysis and adenosine triphosphate (ATP) generation. Furthermore, two haloacid dehalogenase-like phosphatases (PA0562 and PA3172) that play roles in the dephosphorylation of G3P in strain PAO1 were identified, and their enzymatic properties were characterized. Our findings reveal the importance of G3P homeostasis and indicate that GlpD, the key enzyme for G3P catabolism, is a potential therapeutic target for the prevention and treatment of infections by this pathogen.
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影响因子：
5.6
作者：
Jurado-Martín I;Sainz-Mejías M;McClean S
通讯作者：
McClean S
铜绿假单胞菌中的氧化应激反应。
DOI：
10.3390/pathogens10091187
发表时间：
2021-09-14
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
da Cruz Nizer WS;Inkovskiy V;Versey Z;Strempel N;Cassol E;Overhage J
通讯作者：
Overhage J
影响因子：
4.5
作者：
Campilongo R;Fung RKY;Little RH;Grenga L;Trampari E;Pepe S;Chandra G;Stevenson CEM;Roncarati D;Malone JG
通讯作者：
Malone JG
影响因子：
3.6
作者：
Dietrich, Lars E. P.;Price-Whelan, Alexa;Newman, Dianne K.
通讯作者：
Newman, Dianne K.
影响因子：
3.2
作者：
ESSAR, DW;EBERLY, L;CRAWFORD, IP
通讯作者：
CRAWFORD, IP