Deletion of the L-Lactate Dehydrogenase Gene ldh in Streptococcus pyogenes 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 ha...

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Published in:Frontiers in microbiology Vol. 8; p. 1841
Main Authors: Oehmcke-Hecht, Sonja, Nass, Leif E, Wichura, Jan B, Mikkat, Stefan, Kreikemeyer, Bernd, Fiedler, Tomas
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 21-09-2017
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Summary: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.
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Edited by: Fumito Maruyama, Kyoto University, Japan
This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology
Reviewed by: Maren Von Köckritz-Blickwede, University of Veterinary Medicine Hannover, Germany; Shivangi Agarwal, Northwestern University, United States
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2017.01841