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Andries van Mourik

Tuesday 22 February 2011

Host adaptation mechanisms and transcriptional regulation in Campylobacter jejuni

Promotor: Prof.dr J.P.M van Putten
Defence: 22 February 2011
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Bacterial pathogens often contain multiple virulence factors that enable infection of distinct anatomical niches in different host species. The expression of virulence factors is usually tightly regulated probably to prevent their unnecessary production and to escape neutralization by the host immune system. Classical virulence factors as present in the common enteropathogens such as Salmonella and Shigella spp. are bacterial adhesins, invasins, type III secretion systems, and secreted toxins (10, 15, 18, 22, 49). Campylobacter jejuni is the most common cause of bacterial foodborne illness causing >100 million human cases each year (3, 19). In contrast to other enteropathogens, C. jejuni appears to lack the set of classical virulence traits but is equipped with a large repertoire of adaptation skills that influence bacterial surface properties, metabolism and behavior. This environmental adaptation may contribute to bacterial virulence by enabling the bacteria to rapidly alter their phenotype and metabolism in response to changes in host environment. The well developed adaptation of C. jejuni is illustrated by the presence of a highly branched electron transport system that is important for the ability of C. jejuni to colonize chickens (25, 50, 52). Transcriptome analysis further confirmed large differences in C. jejuni gene transcription under in vitro and in vivo growth conditions (46, 53). Despite their importance the knowledge regarding the adaptation and signal transduction system(s) that direct the environmental adaptation in C. jejuni is limited. In this thesis I describe three novel C. jejuni adaptation mechanisms and investigated their function in the regulation of bacterial behavior.

In Chapter 2 the discovery and characterization of a functional C. jejuni Tat secretion machinery is described. This system is necessary for the transport of different proteins essential for adaptation to nutrient and oxygen limited conditions. In Chapter 3 the existence in C. jejuni of two novel complementary lipid A modifying enzymes and their function as an immune modulatory system are described. Analysis of the function of two-component systems as regulators of bacterial metabolism revealed that the Dsb system of C. jejuni is important for the function of the RacS sensor protein (Chapter 4) and that the two-component system RacS-RacR regulates metabolic processes during conditions of oxygen limitation (Chapter 5). In this chapter (Chapter 6) the most important findings are summarized and discussed.