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Title: Functional analysis of PBP2b in Bacillus subtilis
Author: Xu, Meizhu
ISNI:       0000 0001 3573 9073
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2008
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The major structural component of the eubacterial cell wall is a net like matrix of peptidoglycan (PG). The final steps of PG assembly are carried out by a large family of penicillin-binding proteins (PBPs). Some PBPs are redundant, but most bacteria have an essential PBP specialised for cell division. PBP2b of B. sllbtilis is essential for cell division and it targets division sites by interaction with one or more components of the division machinery. The aim of the work described in this thesis was to understand the function ofPBP2b in the cell cycle ofB. sllbtilis. Remarkably, substitution of the catalytic serine of PBP2b had almost no effect on cell division in B. sllbtilis, even though depletion of the entire protein is lethal. Further analysis of the catalytically inactive form of PBP2b revealed that PBP3, previously shown to be dispensable, took on an essential role. This study also revealed that the essential function of PBP3, in the absence of biochemically active PBP2b, lies in its transpeptidase (TPase) activity. Overall, this research suggests that the division machinery is constructed in such a way that if the primary TPase activity of the architectural PBP2b enzyme is inactivated, a secondary, non-architectural PBP (PBP3) can access the site and provide a back-up TPase that will allow the septum to be completed. This has interesting parallels with the mechanism of methicillin-resistance in Staphylococcus aureus (MRSA). In further studies, the combination of PBP2b Ts mutations with the divIB, divIC, andftsL mutation backgrounds suggested that different parts of the N-terrninal domain of PBP2b may be involved in interactions with specific division proteins. In addition, although the TPase function is not essential, the TPase domain may be involved in the interaction with other division proteins. The C-terminal domain of PBP2b was shown to be inessential for vegetative cell growth and sporulation at 'permissive temperatures. Its function is probably to stabilize PBP2b at elevated temperatures. Previous research suggested that that PBP2b may take part in the early stages of sporulation. In this thesis, its function has been further investigated and the results suggest that PBP2b may be also involved in the late stages of sporulation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available