pestis, the causative agent of plague, and two enteric pathogens, Y. pseudotuberculosis and Y. enterocolitica. Despite the differences in disease, Y. pestis and Y. pseudotuberculosis are

very closely related at the genetic level. Y. pestis is believed to have evolved from Y. pseudotuberculosis between 1,500-20,000 years ago [1]. Thus, in a remarkably short length of evolutionary time, Y. pestis has evolved from an enteropathogen, to a blood-borne pathogen with an insect vector [2]. Genome sequencing of several Y. pseudotuberculosis and Y. pestis strains, revealed that Y. pestis has accumulated a large number of pseudogenes since its divergence. By the “”use it or lose it”" paradigm, this is suggestive of the decay of those genes that are no longer required for function as Y. pestis adapts to a new lifestyle [3, 4]. Gene disruption may also result in pathoadaptive mutation, whereby loss of gene selleckchem function results in an increase

in virulence [5]. This has been demonstrated in several pathogenic bacteria including Shigella spp. and Escherichia selleck products coli [6, 7]. Pathoadaptive mutations have previously been identified in Y. pestis, with the negative regulators of biofilm formation, rcsA and nghA, being disrupted, resulting in the ability of Y. pestis to form biofilms within the flea vector [8, 9]. Pseudogenes in Y. pestis that are known to be essential for the enteric lifestyle of Y. pseudotuberculosis, include the adhesins YadA and invasin [3, 10, 11]. Invasin was one of the first bacterial virulence factors identified, when it was observed that the inv gene alone was sufficient to convert benign non-invasive laboratory E. coli strains, to being capable of invading tissue culture cells [12]. Invasin is a 103 kDa protein that is capable of binding to β1 integrins on the host cells, promoting internalisation of the bacterium [13]. During early

infection, invasin specifically binds β1 integrins on the apical surface of M cells, which facilitates efficient translocation to the underlying Peyer’s patches [14]. The invasin protein is composed of a short N-terminal transmembrane domain, four structural bacterial immunoglobulin domains (bIg domains) and a C-type lectin-like domain [15]. The last bIg domain and the C-type lectin-like domain comprise the functional β1 integrin Tau-protein kinase binding region [15, 16]. In the same family of bacterial adhesion proteins as invasin, is intimin, an important adhesin expressed by enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) E. coli on the LEE pathogenicity island [17]. Intimin is a 94 kDa outer membrane protein that is also found in Citrobacter freundii and Hafnia alvei [17, 18]. The functional binding domain of intimin is located in the 280 amino acid C-terminal region, and consists of two bIg domains and a C-type lectin-like domain, which are structurally similar to invasin [15, 18, 19].