SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>

ABSTRACT The membrane protease SppA of Bacillus subtilis was first described as a signal peptide peptidase and later shown to confer resistance to lantibiotics. Here, we report that SppA forms octameric complexes with YteJ, a membrane protein of thus-far-unknown function. Interestingly, sppA and yte...

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Autores principales:	Gabriela Henriques, Stephen McGovern, Jolanda Neef, Minia Antelo-Varela, Friedrich Götz, Andreas Otto, Dörte Becher, Jan Maarten van Dijl, Matthieu Jules, Olivier Delumeau
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Bacillus subtilis signal peptide peptidase lantibiotic resistance membrane protein complex enzymatic regulation proteases Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/86d628bcbe9b4787845a27416dca1935
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spelling	oai:doaj.org-article:86d628bcbe9b4787845a27416dca19352021-11-15T15:30:58ZSppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>10.1128/mSphere.00724-202379-5042https://doaj.org/article/86d628bcbe9b4787845a27416dca19352020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00724-20https://doaj.org/toc/2379-5042ABSTRACT The membrane protease SppA of Bacillus subtilis was first described as a signal peptide peptidase and later shown to confer resistance to lantibiotics. Here, we report that SppA forms octameric complexes with YteJ, a membrane protein of thus-far-unknown function. Interestingly, sppA and yteJ deletion mutants exhibited no protein secretion defects. However, these mutant strains differed significantly in their resistance to antimicrobial peptides. In particular, sppA mutant cells displayed increased sensitivity to the lantibiotics nisin and subtilin and the human lysozyme-derived cationic antimicrobial peptide LP9. Importantly, YteJ was shown to antagonize SppA activity both in vivo and in vitro, and this SppA-inhibitory activity involved the C-terminal domain of YteJ, which was therefore renamed SppI. Most likely, SppI-mediated control is needed to protect B. subtilis against the potentially detrimental protease activity of SppA since a mutant overexpressing sppA by itself displayed defects in cell division. Altogether, we conclude that the SppA-SppI complex of B. subtilis has a major role in protection against antimicrobial peptides. IMPORTANCE Our study presents new insights into the molecular mechanism that regulates the activity of SppA, a widely conserved bacterial membrane protease. We show that the membrane proteins SppA and SppI form a complex in the Gram-positive model bacterium B. subtilis and that SppI inhibits SppA protease activity in vitro and in vivo. Furthermore, we demonstrate that the C-terminal domain of SppI is involved in SppA inhibition. Since SppA, through its protease activity, contributes directly to resistance to lantibiotic peptides and cationic antibacterial peptides, we propose that the conserved SppA-SppI complex could play a major role in the evasion of bactericidal peptides, including those produced as part of human innate immune defenses.Gabriela HenriquesStephen McGovernJolanda NeefMinia Antelo-VarelaFriedrich GötzAndreas OttoDörte BecherJan Maarten van DijlMatthieu JulesOlivier DelumeauAmerican Society for MicrobiologyarticleBacillus subtilissignal peptide peptidaselantibiotic resistancemembrane protein complexenzymatic regulationproteasesMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bacillus subtilis signal peptide peptidase lantibiotic resistance membrane protein complex enzymatic regulation proteases Microbiology QR1-502
spellingShingle	Bacillus subtilis signal peptide peptidase lantibiotic resistance membrane protein complex enzymatic regulation proteases Microbiology QR1-502 Gabriela Henriques Stephen McGovern Jolanda Neef Minia Antelo-Varela Friedrich Götz Andreas Otto Dörte Becher Jan Maarten van Dijl Matthieu Jules Olivier Delumeau SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>
description	ABSTRACT The membrane protease SppA of Bacillus subtilis was first described as a signal peptide peptidase and later shown to confer resistance to lantibiotics. Here, we report that SppA forms octameric complexes with YteJ, a membrane protein of thus-far-unknown function. Interestingly, sppA and yteJ deletion mutants exhibited no protein secretion defects. However, these mutant strains differed significantly in their resistance to antimicrobial peptides. In particular, sppA mutant cells displayed increased sensitivity to the lantibiotics nisin and subtilin and the human lysozyme-derived cationic antimicrobial peptide LP9. Importantly, YteJ was shown to antagonize SppA activity both in vivo and in vitro, and this SppA-inhibitory activity involved the C-terminal domain of YteJ, which was therefore renamed SppI. Most likely, SppI-mediated control is needed to protect B. subtilis against the potentially detrimental protease activity of SppA since a mutant overexpressing sppA by itself displayed defects in cell division. Altogether, we conclude that the SppA-SppI complex of B. subtilis has a major role in protection against antimicrobial peptides. IMPORTANCE Our study presents new insights into the molecular mechanism that regulates the activity of SppA, a widely conserved bacterial membrane protease. We show that the membrane proteins SppA and SppI form a complex in the Gram-positive model bacterium B. subtilis and that SppI inhibits SppA protease activity in vitro and in vivo. Furthermore, we demonstrate that the C-terminal domain of SppI is involved in SppA inhibition. Since SppA, through its protease activity, contributes directly to resistance to lantibiotic peptides and cationic antibacterial peptides, we propose that the conserved SppA-SppI complex could play a major role in the evasion of bactericidal peptides, including those produced as part of human innate immune defenses.
format	article
author	Gabriela Henriques Stephen McGovern Jolanda Neef Minia Antelo-Varela Friedrich Götz Andreas Otto Dörte Becher Jan Maarten van Dijl Matthieu Jules Olivier Delumeau
author_facet	Gabriela Henriques Stephen McGovern Jolanda Neef Minia Antelo-Varela Friedrich Götz Andreas Otto Dörte Becher Jan Maarten van Dijl Matthieu Jules Olivier Delumeau
author_sort	Gabriela Henriques
title	SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_short	SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_full	SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_fullStr	SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_full_unstemmed	SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_sort	sppi forms a membrane protein complex with sppa and inhibits its protease activity in <named-content content-type="genus-species">bacillus subtilis</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/86d628bcbe9b4787845a27416dca1935
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SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>

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