Depke Tobias, Häussler Susanne, Brönstrup Mark
Department of Chemical Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Institute of Molecular Bacteriology, Twincore, Centre for Clinical and Experimental Infection Research, 30625 Hannover, Germany.
Metabolites. 2020 Oct 18;10(10):417. doi: 10.3390/metabo10100417.
is one of the most important nosocomial pathogens and understanding its virulence is the key to effective control of infections. The regulatory network governing virulence factor production in is exceptionally complex. Previous studies have shown that the peptide chain release factor methyltransferase PrmC plays an important role in bacterial pathogenicity. Yet, the underlying molecular mechanism is incompletely understood. In this study, we used untargeted liquid and gas chromatography coupled to mass spectrometry to characterise the metabolome of a defective PA14 strain in comparison with the corresponding strain complemented with . The comprehensive metabolomics data provided new insight into the influence of on virulence and metabolism. deficiency had broad effects on the endo- and exometabolome of PA14, with a marked decrease of the levels of aromatic compounds accompanied by reduced precursor supply from the shikimate pathway. Furthermore, a pronounced decrease of phenazine production was observed as well as lower abundance of alkylquinolones. Unexpectedly, the metabolomics data showed no -dependent effect on rhamnolipid production and an increase in pyochelin levels. A putative virulence biomarker identified in a previous study was significantly less abundant in the deficient strain.
是最重要的医院病原体之一,了解其毒力是有效控制感染的关键。控制毒力因子产生的调控网络异常复杂。先前的研究表明,肽链释放因子甲基转移酶PrmC在细菌致病性中起重要作用。然而,其潜在的分子机制尚未完全了解。在本研究中,我们使用非靶向液相色谱和气相色谱联用质谱法,对缺失的PA14菌株的代谢组进行了表征,并与补充了的相应菌株进行了比较。全面的代谢组学数据为对毒力和代谢的影响提供了新的见解。缺失对PA14的内代谢组和外代谢组有广泛影响,芳香族化合物水平显著降低,同时莽草酸途径的前体供应减少。此外,还观察到吩嗪产量明显下降以及烷基喹诺酮丰度降低。出乎意料的是,代谢组学数据显示对鼠李糖脂的产生没有依赖性影响,并且绿脓菌素水平增加。先前研究中鉴定的一种假定的毒力生物标志物在缺失菌株中的丰度显著降低。