Peptidoglycan degradation machinery in Clostridium difficile forespore engulfment. Issue 3 (30th October 2018)

• Record Type: Journal Article
• Authors: Dembek, Marcin; Kelly, Abigail; Barwinska‐Sendra, Anna; Tarrant, Emma; Stanley, Will A.; Vollmer, Daniela; Biboy, Jacob; Gray, Joe; Vollmer, Waldemar; Salgado, Paula S.
• Is Part Of: Molecular microbiology. Volume 110:Issue 3(2018)
• Page Start: 390
• Page End: 410
• Publication Date: 2018-10-30
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14091
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: Clostridium difficile remains the leading cause of antibiotic‐associated diarrhoea in hospitals worldwide, linked to significant morbidity and mortality. As a strict anaerobe, it produces dormant cell forms – spores – which allow it to survive in the aerobic environment. Importantly, spores are the transmission agent of C. difficile infections. A key aspect of sporulation is the engulfment of the future spore by the mother cell and several proteins have been proposed to be involved. Here, we investigated the role of the SpoIID, SpoIIM and SpoIIP (DMP) machinery and its interplay with the SpoIIQ:SpoIIIAH (Q:AH) complex in C. difficile . We show that, surprisingly, SpoIIM, the proposed machinery anchor, is not required for efficient engulfment and sporulation. We demonstrate the requirement of DP for engulfment due to their sequential peptidoglycan degradation activity, both in vitro and in vivo . Finally, new interactions within DMP and between DMP and Q:AH suggest that both systems form a single engulfment machinery to keep the mother cell and forespore membranes together throughout engulfment. This work sheds new light upon the engulfment process and on how different sporeformers might use the same components in different ways to drive spore formation. Abstract : Clostridium difficile is a major cause of antibiotic related diarrhoea. C. difficile infections spread via spores, a highly resistant dormant cell form that involves a small cell being engulfed by a larger cell. We show evidence of a novel organisation of the protein machinery driving this process: two protein complexes (DP and Q:AH) act concertedly to keep the membranes tightly together as sequential enzymatic activity of SpoIIP and SpoIID drives engulfment.