The acid tolerance response of enteropathogenic Salmonella and Escherichia coli strains : A proteomic characterisation and novel links with motility and virulence

Abstract

This thesis concentrates on elucidating the mechanisms involved in the adaptation of exponentially growing EPEC and Salmonellai to inorganic and weak organic acids. An understanding of these mechanisms, collectively known as the acid tolerance response (ATR) is of relevance to both the food production and medicinal industries.

One of the most striking findings is that flagellin, the major structural component of the bacterial flagellum, is down-regulated at pH 3.0 in acid adapted Salmonella. Further studies using reporter gene fusions indicate that the entire flagellar apparatus is transcriptionally repressed under these conditions. PhoPQ is found to mediate this mechanism, which results in a loss of cell motility, by acting directly or indirectly at the level of the flagellar fhCD master operon.

One of the most striking findings is that flagellin, the major structural component of the bacterial flagellum, is down-regulated at pH 3.0 in acid adapted Salmonella. Further studies using reporter gene fusions indicate that the entire flagellar apparatus is transcriptionally repressed under these conditions. PhoPQ is found to mediate this mechanism, which results in a loss of cell motility, by acting directly or indirectly at the level of the flagellar flhCD master operon.

Additional links between other virulence associated mechanisms and the ATR are also investigated. 2 ATR proteins regulated by PhoPQ are expressed similarly during the oxidative stress response. Correspondingly, survival assays indicate that an acid induced cross protection of oxidative stress in Salmonella is mediated by this global regulator. A further two regulators of pathogenesis (the BipA GTPase and the EAF plasmid) are characterised as negative regulators of the ATR in certain EPEC strains. It is concluded that ATR mechanisms are variable between different species and strains.

Based on these results, it is proposed that intimate connections exist between the regulation of the ATR and virulence associated processes, such as motility, that are essential for pathogenesis. The full elucidation of the mechanisms behind the regulation and implementation of these systems may pave the way for future treatments of food-borne disease. The global regulatory molecules involved constitute putative drug targets.

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