Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.785806
Title: MreB dependent cell envelope homeostasis in Bacillus subtilis
Author: Seistrup, Kenneth Holst
ISNI:       0000 0004 7971 3002
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2019
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Abstract:
One of the hallmarks of cellular life is the protective membrane. The membrane not only encapsulates the nutrient rich cytoplasm, but also facilitates many important processes essential for most biological life such as the ATP producing oxidative phosphorylation, meaning that tight regulation of membrane homeostasis must be sustained. In Bacteria the membrane is also home to the final stages of peptidoglycan synthesis, thus coupling cell wall production and the membrane. The protein governing where the insertion of new peptidoglycan occurs in rod-shaped Bacteria is the actin homologue MreB (Errington, 2015). Previous studies have suggested that MreB and its homologues are involved in cell envelope homeostasis, not only through fatty acid adaptations, but through regulation of peptidoglycan degrading autolysins as well (Dominguez-Cuevas et al., 2013; Strahl et al., 2014). In this thesis I aimed to describe which homeostatic changes occur within the membrane when deleting the MreB cytoskeleton, as well as describe if these changes alter the physical parameters associated with fluidity and temperature dependent growth phenotypes. Additionally, I wanted to elucidate if the deletion of mreB and its homologues changes the sequence of actions following disruptions to membrane homeostasis such as dissipation of membrane potential, which under normal circumstances rigidifies the membrane, delocalizes multiple membrane associated proteins, and eventually induces lysis (Strahl and Hamoen, 2010). Through fatty acid analysis in multiple MreB cytoskeletal mutants I found that the lack of MreB and its homologues lead to altered fatty acid composition, which in turn causes membrane fluidity to be altered in a complex manner, indicating that MreB is important in maintaining a well-coordinated membrane homeostasis. Additionally, I examined membrane rigidification caused by membrane depolarization, and discovered that MreB was not involved, but rather electrostriction was the most likely candidate. Finally, through lysis assays and microscopy I examined membrane depolarization induced lysis. I found that the lysis is caused by MreB being delocalized, thus redirecting the cell wall synthesis machinery and mis-regulating autolysins essential for efficient membrane elongation, finally causing loss of communication between anabolism and catabolism of the cell wall. Together, these findings elucidate the important role MreB occupies in the membrane, not only guiding the cell elongasome, but in maintaining well-coordinated membrane homeostasis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.785806  DOI: Not available
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