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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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-10-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00724-20 |
| _version_ | 1818427858076303360 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:52:24Z |
| format | Article |
| id | doaj.art-86d628bcbe9b4787845a27416dca1935 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-14T14:52:24Z |
| publishDate | 2020-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-86d628bcbe9b4787845a27416dca19352022-12-21T22:57:06ZengAmerican Society for MicrobiologymSphere2379-50422020-10-015510.1128/mSphere.00724-20SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <named-content content-type="genus-species">Bacillus subtilis</named-content>Gabriela Henriques0Stephen McGovern1Jolanda Neef2Minia Antelo-Varela3Friedrich Götz4Andreas Otto5Dörte Becher6Jan Maarten van Dijl7Matthieu Jules8Olivier Delumeau9Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversity of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Groningen, The NetherlandsUniversity of Greifswald, Centre of Functional Genomics of Microbes, Institute of Microbiology, Department of Microbial Proteomics, Greifswald, GermanyDepartment of Microbial Genetics, University of Tübingen, Tübingen, GermanyUniversity of Greifswald, Centre of Functional Genomics of Microbes, Institute of Microbiology, Department of Microbial Proteomics, Greifswald, GermanyUniversity of Greifswald, Centre of Functional Genomics of Microbes, Institute of Microbiology, Department of Microbial Proteomics, Greifswald, GermanyUniversity of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Groningen, The NetherlandsUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00724-20Bacillus subtilissignal peptide peptidaselantibiotic resistancemembrane protein complexenzymatic regulationproteases |
| spellingShingle | 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> mSphere Bacillus subtilis signal peptide peptidase lantibiotic resistance membrane protein complex enzymatic regulation proteases |
| 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_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_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_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 |
| topic | Bacillus subtilis signal peptide peptidase lantibiotic resistance membrane protein complex enzymatic regulation proteases |
| url | https://journals.asm.org/doi/10.1128/mSphere.00724-20 |
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