%A Oehmcke-Hecht,Sonja %A Nass,Leif E. %A Wichura,Jan B. %A Mikkat,Stefan %A Kreikemeyer,Bernd %A Fiedler,Tomas %D 2017 %J Frontiers in Microbiology %C %F %G English %K SpeB,LDH,Galleria mellonella,Streptococcus pyogenes,contact system %Q %R 10.3389/fmicb.2017.01841 %W %L %M %P %7 %8 2017-September-21 %9 Original Research %+ Tomas Fiedler,Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre,Rostock, Germany,tomas.fiedler@med.uni-rostock.de %# %! Loss of SpeB activity in a S. pyogenes ldh deletion mutant %* %< %T Deletion of the L-Lactate Dehydrogenase Gene ldh in Streptococcus pyogenes Leads to a Loss of SpeB Activity and a Hypovirulent Phenotype %U https://www.frontiersin.org/articles/10.3389/fmicb.2017.01841 %V 8 %0 JOURNAL ARTICLE %@ 1664-302X %X Streptococcus pyogenes uses lactic acid fermentation for the generation of ATP. Here, we analyzed the impact of a deletion of the L-lactate dehydrogenase gene ldh on the virulence of S. pyogenes M49. While the ldh deletion does not cause a general growth deficiency in laboratory media, the growth in human blood and plasma is significantly hampered. The ldh deletion strain is furthermore less virulent in a Galleria mellonella infection model. We show that the ldh deletion leads to a decrease in the activity of the cysteine protease SpeB, an important secreted virulence factor of S. pyogenes. 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 S. pyogenes. All these effects can be reversed when ldh is reintroduced into the mutant via a plasmid. The results demonstrate a previously unappreciated role for LDH in modulation of SpeB maturation.