Cancelled | [SCAN] A develpmental checkpoint protein that licenses the final stages in the assembly of the Clostridiodes difficile spores surface

Title: A develpmental checkpoint protein that licenses the final stages in the assembly of the Clostridiodes difficile spores surface

Speaker: Adriano Henriques    

From: Microbial Development Lab, ITQB NOVA

Abstract: A pivotal event in spore development in the pathogen Clostridiodes difficile occurs when the forespore is engulfed by the mother cell and released as an independent protoplast within the mother-cell cytoplasm. This developmental transition activates the transcription factor σK, which programs RNA polymerase to transcribe late sporulation genes, including yabG, encoding a cysteine protease essential for spore maturation.

YabG possesses a unique architecture, comprising an N-terminal SH3b domain linked to a CheY-like catalytic domain, a combination conserved across spore-forming bacteria but unprecedented among cysteine proteases.

To ensure precise substrate processing, YabG activity is subject to multiple layers of regulation. Its production is confined to the mother cell and initiated only after forespore engulfment, restricting proteolysis to the late stages of sporulation. YabG is recruited to the developing spore surface through interactions with pre-assembled substrates, which include proteins required for spore assembly, spore germination and host colonization. Localization through substrate interactions spatially restricts the activity of YabG. Finally, an autoproteolytic activity provides an additional safeguard against premature or inappropriate protease activity.

Strikingly, beyond its proteolytic role, YabG is also required for the expression of at least two genes encoding major spore surface components, revealing an unexpected contribution to the regulation of late sporulation.

By integrating protein maturation with gene expression, YabG orchestrates the final assembly of the Clostridioides difficile spore surface, generating spores that are structurally resilient and fully competent for germination and host colonization.

Here, we present our ongoing efforts to uncover the structural basis of YabG function, to define the molecular mechanisms underlying substrate recognition and processing, and its unexpected role in transcriptional regulation.

SCANs are weekly seminars that happen every Wednesday at noon by in-house researchers and invited speakers at ITQB NOVA.