The role of outer membrane homeostasis in the virulence of gram-negative bacteria

Morris, Faye Christina (2014). The role of outer membrane homeostasis in the virulence of gram-negative bacteria. University of Birmingham. Ph.D.

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Abstract

his study investigated the underlying mechanisms of outer membrane homeostasis in Gram-negative bacteria. Using both the evolved laboratory strain E. coli K12 and the broad host range pathogen Salmonella enterica serovar Typhimurium, we have identified and characterised a series of non-essential genes responsible for the maintenance of the outer membrane barrier function. We have revealed their importance for bacterial pathogenesis suggesting their use as novel targets for drug development. This study has provided the first description of a pathway for phospholipid transport from the inner membrane to the outer membrane via the lipoprotein PlpA, a gene previously of unknown function. As several of the genes highlighted by our initial studies were associated with the biogenesis of virulence factors, we complemented our investigations by characterising the contributions of the S. Typhimurium Type V proteins to virulence in a murine model. These investigations have provided the first peer reviewed characterisation of a trimeric autotransporter from Salmonella, has identified a mechanism by which Salmonella can survive on tomatoes, and has highlighted the functional redundancy of these proteins in Salmonella infection. These findings have significantly advanced our understanding of the mechanisms mediating outer membrane homeostasis and the biogenesis and functions of virulence factors.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):