Penicillin-binding proteins exhibit functional redundancy during asymmetric cell division in Clostridioides difficile

Area of Science:

• Bacterial cell wall synthesis
• Microbial cell division
• Bacterial sporulation

Background:

• Peptidoglycan synthesis is vital for bacterial growth and division, involving glycosyltransferases and penicillin-binding proteins (PBPs).
• Some PBPs exhibit functional redundancy, especially under cell wall stress, but the mechanisms remain incompletely understood.
• Endospore-forming bacteria utilize multiple PBPs for complex morphological changes during sporulation.

Purpose of the Study:

• To investigate the role and functional redundancy of the sporulation-specific PBP, SpoVD, in *Clostridioides difficile* sporulation.
• To elucidate the mechanisms underlying compensatory PBP functions during bacterial cell division and differentiation.

Main Methods:

• Genetic analysis of *Clostridioides difficile* sporulation mutants.
• Localization studies of PBPs at the polar division septum.
• Biochemical assays to assess PBP catalytic activity and interactions.

Main Results:

• SpoVD's catalytic activity is essential for cortex synthesis but partially dispensable for asymmetric division during sporulation.
• The SEDS partner SpoVE and another sporulation-induced PBP, PBP3, are required for SpoVD's dispensability in division.
• PBP3 promotes division independently of its catalytic activity, a novel mechanism of functional redundancy.

Conclusions:

• Functional redundancy in PBPs can occur through diverse mechanisms beyond catalytic activity.
• PBP3's non-catalytic role in division highlights unique compensatory strategies in bacterial sporulation.
• Understanding these redundancies is crucial for deciphering bacterial cell wall dynamics and potential antibiotic resistance.