Claude McKay and the transnational novel

This thesis considers the three works of fiction of the Jamaican author Claude McKay (1889-1948) as a coherent transnational trilogy which dramatises the semi-autobiographical complexities of diasporic exile and return in the period of the 1920s and 1930s. Chapter One explores McKay’s urban North American novel, Home to Harlem (1928). I suggest that we need to ‘reworld’ conceptions of McKay’s writing in order to release him from his canonical confinement in the Harlem Renaissance. Querying the problematics of the city space, of sexuality and of race as they emerge in the novel, this chapter considers McKay’s percipient understanding of the need to reconfigure diasporic identity beyond the limits set by American nationalism. Chapter Two engages with McKay’s novel of portside Marseilles, Banjo (1929), and considers the homosocial interactions of the vagabond collective. A comparison of North America and France as supposed exemplars of individual liberty highlights the unsuitability of nationalistic prerogatives to an internally diverse black diaspora. Paul Gilroy’s Black Atlantic construct provides a suggestive space in which to re-imagine the possibilities of affiliation in the port. The latter section of the chapter examines McKay’s particular influence on, and relationship, to the Négritude movement and Pan-African philosophies. Chapter Three focuses on McKay’s third novel, Banana Bottom (1933). I suggest here that the three novels comprise a coherent New World Trilogy comparable to Edward (Kamau) Brathwaite’s trilogy, The Arrivants. This chapter considers both the Caribbean and the transnational dimensions to McKay’s work.

The role of metabolism in the pathogenesis of adherent invasive Escherichia coli (AIEC)

Crohn’s disease (CD) is a chronic, relapsing inflammatory condition affecting the gastrointestinal tract of humans, of which there is currently no cure. The precise etiology of CD is unknown, although it has become widely accepted that it is a multifactorial disease which occurs as a result of an abnormal immune response to commensal enteric bacteria in a genetically susceptible host. Recent studies have shown that a new group of Escherichia coli, called Adherent Invasive Escherichia coli (AIEC) are present in the guts of CD patients at a higher frequency than in healthy subjects, suggesting that they may play a role in the initiation and/or maintenance of the inflammation associated with CD. Two phenotypes define an AIEC and differentiate them from other groups of E. coli. Firstly, AIEC can adhere to and invade epithelial cells; and secondly, they can replicate in macrophages. In this study, we use a strain of AIEC which has been isolated from the colonic mucosa of a CD patient, called HM605, to examine the relationship between AIEC and the macrophage. We show, using a systematic mutational approach, that while the Tricarboxylic acid (TCA) cycle, the glyoxylate pathway, the Entner-Doudoroff (ED) pathway, the Pentose Phosphate (PP) pathway and gluconeogenesis are dispensable for the intramacrophagic growth of HM605, glycolysis is an absolute requirement for the ability of this organism to replicate intracellularly. We also show that HM605 activates the inflammasome, a major driver of inflammation in mammals. Specifically, we show that macrophages infected with HM605 produce significantly higher levels of the pro-inflammatory cytokine IL-1β than macrophages infected with a non-AIEC strain, and we show by immunoblotting that this is due to cleavage of caspase-1. We also show that macrophages infected with HM605 exhibit significantly higher levels of pyroptosis, a form of inflammatory cell death, than macrophages infected with a non-AIEC strain. Therefore, AIEC strains are more pro-inflammatory than non-AIEC strains and this may have important consequences in terms of CD pathology. Moreover, we show that while inflammasome activation by HM605 is independent of intracellular bacterial replication, it is dependent on an active bacterial metabolism. Through the establishment of a genetic screen aimed at identifying mutants which activate the inflammasome to lower levels than the wild-type, we confirm our observation that bacterial metabolism is essential for successful inflammasome activation by HM605 and we also uncover new systems/structures that may be important for inflammasome activation, such as the BasS/BasR two-component system, a type VI secretion system and a K1 capsule. Finally, in this study, we also identify a putative small RNA in AIEC strain LF82, which may be involved in modulating the motility of this strain. Overall this works shows that, in the absence of specialised virulence factors, the ability of AIEC to metabolise within the host cell may be a key determinant of its pathogenesis.