Sppl Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in Bacillus subtilis

Gabriela Henriques, Stephen McGovern, Jolanda Neef, Minia Antelo-Varela, Friedrich Goetz, Andreas Otto, Doerte Becher, Jan Maarten van Dijl, Matthieu Jules, Olivier Delumeau*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
35 Downloads (Pure)


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 yid 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 Sppl. Most likely, Sppl-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-Sppl complex of B. subtills 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 Sppl form a complex in the Gram-positive model bacterium B. subtilis and that Sppl inhibits SppA protease activity in vitro and in vivo. Furthermore, we demonstrate that the C-terminal domain of Sppl 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-Sppl complex could play a major role in the evasion of bactericidal peptides, including those produced as part of human innate immune defenses.

Original languageEnglish
Article numberARTN e00724-20
Number of pages16
Issue number5
Publication statusPublished - 2020


  • Bacillus subtilis
  • signal peptide peptidase
  • lantibiotic resistance
  • membrane protein complex
  • enzymatic regulation
  • proteases
  • FTSH

Cite this