Oehmcke-Hecht Sonja, Nass Leif E, Wichura Jan B, Mikkat Stefan, Kreikemeyer Bernd, Fiedler Tomas
Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical CentreRostock, Germany.
Core Facility Proteome Analysis, Rostock University Medical CentreRostock, Germany.
Front Microbiol. 2017 Sep 21;8:1841. doi: 10.3389/fmicb.2017.01841. eCollection 2017.
uses lactic acid fermentation for the generation of ATP. Here, we analyzed the impact of a deletion of the L-lactate dehydrogenase gene on the virulence of M49. While the deletion does not cause a general growth deficiency in laboratory media, the growth in human blood and plasma is significantly hampered. The deletion strain is furthermore less virulent in a infection model. We show that the deletion leads to a decrease in the activity of the cysteine protease SpeB, an important secreted virulence factor of . The reduced SpeB activity is caused by a hampered autocatalytic activation of the SpeB zymogen into the mature SpeB. The missing SpeB activity furthermore leads to increased plasmin activation and a reduced activation of the contact system on the surface of . All these effects can be reversed when is reintroduced into the mutant via a plasmid. The results demonstrate a previously unappreciated role for LDH in modulation of SpeB maturation.
利用乳酸发酵来生成三磷酸腺苷（ATP）。在此，我们分析了L - 乳酸脱氢酶基因缺失对M49毒力的影响。虽然该缺失在实验室培养基中不会导致普遍的生长缺陷，但在人血液和血浆中的生长却受到显著阻碍。此外，缺失菌株在感染模型中的毒力较低。我们表明，该缺失导致半胱氨酸蛋白酶SpeB（一种重要的分泌型毒力因子）的活性降低。SpeB活性降低是由于SpeB酶原向成熟SpeB的自催化激活受阻所致。缺失的SpeB活性还导致纤溶酶激活增加以及在其表面接触系统的激活减少。当通过质粒将其重新引入突变体时，所有这些效应都可以逆转。结果证明了乳酸脱氢酶（LDH）在调节SpeB成熟方面以前未被认识到的作用。
