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Title: Structural investigation of the evolution, mechanism and assembly of the flagellar motor
Author: Ferreira, Josie Liane
ISNI:       0000 0004 9350 7352
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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The evolution of molecular machines is fundamental to the development of pathogenesis in bacteria. This drives the adaptation to new lifestyles and the colonisation of novel niches. One such machine is the bacterial flagellum, an extracellular motility device which enables cells to actively seek out favourable environments. The flagellum is a vital virulence factor in many bacteria including the important human pathogen, Salmonella enterica. Studying the evolution, mechanism, assembly and regulation of the flagellum will shed light on how modifications in this large molecular machine facilitate life in different environments. At the base of the flagellum is the flagellar motor, which converts electrochemical potential, via the stator complexes, into torque. Torque is then transmitted up the periplasmic rod to rotate the extracellular hook, and filament. The -proteobacterium, Salmonella, has a highly dynamic flagellar motor, perfectly poised for encountering different environments. Surprisingly, this gut pathogen has evolved a different mode of swimming and an environmental niche which is distinct from its close aquatic relatives. Here, using a combination of techniques, I studied the flagellar motor in situ and show that Salmonella’s motor is not native but is a -proteobacterial motor acquired from an ancestor of Bordetella. This new, adaptive motor may have provided a selective advantage to enable Salmonella’s enteropathogenic lifestyle. Interestingly, the non-enteric, -proteobacteria that retained native -motors, swim faster than Salmonella but fare poorly in low nutrient environments. I show that these bacteria have a distinct mechanism for down regulation of motility, for entry into a sessile state. These cells eject their flagella in nutrient limited environments and actively plug the partial structure that is left behind in the outer membrane. I next work towards providing a more detailed understanding of the dynamic mechanism of stator complex incorporation, and finally, provide a novel mechanism for the regulation of rod length. Together, enabled by recent technological advances in the field of electron cryotomography, this work provides insight into some of the fundamental outstanding questions into the evolution, mechanism and regulation of the flagellum.
Supervisor: Beeby, Morgan Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral