Impact of Endogenous Pneumococcal Hydrogen Peroxide on the Activity and Release of Pneumolysin

dc.contributor.authorBazant, Jasmin
dc.contributor.authorOtt, Benjamin
dc.contributor.authorHudel, Martina
dc.contributor.authorHain, Torsten
dc.contributor.authorLucas, Rudolf
dc.contributor.authorMraheil, Mobarak Abu
dc.date.accessioned2024-09-30T10:44:58Z
dc.date.available2024-09-30T10:44:58Z
dc.date.issued2023
dc.description.abstractStreptococcus pneumoniae is the leading cause of community-acquired pneumonia. The pore-forming cholesterol-dependent cytolysin (CDC) pneumolysin (PLY) and the physiological metabolite hydrogen peroxide (H2O2) can greatly increase the virulence of pneumococci. Although most studies have focused on the contribution of both virulence factors to the course of pneumococcal infection, it is unknown whether or how H2O2 can affect PLY activity. Of note, S. pneumoniae exploits endogenous H2O2 as an intracellular signalling molecule to modulate the activity of several proteins. Here, we demonstrate that H2O2 negatively affects the haemolytic activity of PLY in a concentration-dependent manner. Prevention of cysteine-dependent sulfenylation upon substitution of the unique and highly conserved cysteine residue to serine in PLY significantly reduces the toxin’s susceptibility to H2O2 treatment and completely abolishes the ability of DTT to activate PLY. We also detect a clear gradual correlation between endogenous H2O2 generation and PLY release, with decreased H2O2 production causing a decline in the release of PLY. Comparative transcriptome sequencing analysis of the wild-type S. pneumoniae strain and three mutants impaired in H2O2 production indicates enhanced expression of several genes involved in peptidoglycan (PG) synthesis and in the production of choline-binding proteins (CPBs). One explanation for the impact of H2O2 on PLY release is the observed upregulation of the PG bridge formation alanyltransferases MurM and MurN, which evidentially negatively affect the PLY release. Our findings shed light on the significance of endogenous pneumococcal H2O2 in controlling PLY activity and release.en
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG); ROR-ID:018mejw64
dc.identifier.urihttps://jlupub.ub.uni-giessen.de/handle/jlupub/19505
dc.identifier.urihttps://doi.org/10.22029/jlupub-18863
dc.language.isoen
dc.rightsNamensnennung 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddcddc:570
dc.titleImpact of Endogenous Pneumococcal Hydrogen Peroxide on the Activity and Release of Pneumolysin
dc.typearticle
local.affiliationFB 08 - Biologie und Chemie
local.projectSFB TR 84, Funding number 114933180
local.source.articlenumber593
local.source.epage15
local.source.journaltitleToxins
local.source.spage1
local.source.urihttps://doi.org/10.3390/toxins15100593
local.source.volume15

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