Deletion of the L-Lactate Dehydrogenase Gene in Leads to a Loss of SpeB Activity and a Hypovirulent Phenotype.

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.