Despite the fact that E. coli exists as a commensal species in the intestinal microbiota of a variety of animals including humans, not all strains are harmless, and some can cause debilitating and sometimes life-threatening diseases in humans as well as mammals and birds (Belanger et al., 2011). Pathogenic E. coli strains are classified into two groups: those that cause intestinal infection and those that cause extraintestinal infection. Unlike the intestinal commensal E. coli, intestinal pathogenic E. coli strains have acquired virulence-associated genes (VAGs), giving them the ability to cause many serious intestinal diseases (Kaper, Nataro and Mobley, 2004). Among the intestinal E. coli there are eight recognised pathotypes (Fig. 1.2): enteropathogenic
E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EHAC), enterohaemorrhagic (Shiga toxin-producing) E. coli (EHEC/STEC), diffusely adherent E. coli (DAEC), entero-aggregative-haemorrhagic E. coli (EAHEC), and adherent invasive E. coli
(AIEC) (Clements et al., 2012). These pathotypes are capable of causing varying severities of disease ranging from mild, self-limiting diarrhoea to diseases such as haemolytic uraemic syndrome (HUS), which is characterised by haemolytic anaemia, acute kidney failure, and low platelet count. The type of disease caused by an intestinal pathogenic strain of E. coli is influenced by the types of virulence-associated genes that the strain possesses. The profile of VAGs and the type of disease caused by strains is used to broadly classify intestinal E. coli into one of the eight pathotypes, which are used to inform diagnosis and treatment of diseases. There is increasing crossover between E. coli strains of different pathotypes as a result of horizontal recombination, and thus new pathotypes are often proposed, increasing our understanding of the evolution of this important pathogen to humans.
Enteropathogenic E. coli (EPEC) are pathogens that colonise the small intestines and are a common cause of severe, watery diarrhoea in infants of developing countries (Trabulsi, Keller and Tardelli Gomes, 2002). In industrialised countries, the prevalence of these organisms has decreased, but they continue to be an important cause of diarrhoea (Nataro and Kaper, 1998). The primary mechanism of EPEC pathogenesis involves attaching and effacing (A/E) lesions, which are characterised by microvilli destruction, adherence of the bacteria to the intestinal epithelium, pedestal formation, and aggregation of polarised actin and other elements of the cytoskeleton at sites of bacterial attachment (Nataro and Kaper, 1998).
Enterotoxigenic E. coli (ETEC) are strains that colonise the mucosa of the small intestines of humans and cause a mild, self-limiting diarrhoeal disease. In immunocompromised hosts, the disease may progress to a more severe, longer lasting infection akin to that of cholera. ETEC is one of the leading causes of diarrhoea in the developing world, and it is the most common cause
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of travellers’ diarrhoea, a significant disease in children estimated to be responsible for approximately 210 million cases and 380,000 deaths per year (Jelinek and Kollaritsch, 2008). Enteroinvasive E. coli (EIEC) is an intracellular E. coli pathotype which is genetically and biochemically very similar to Shigella, another genus of enteric pathogen within the Enterobacteriaceae. Both EIEC and Shigella possess the ipaH invasive gene (Kaper, Nataro and Mobley, 2004) and cause invasive disease which may lead to severe illness in otherwise healthy individuals. Since EIEC and Shigella are so closely related it has previously been suggested that they should be classified as a single pathotype of E. coli, however Shigella keeps its species designation due to the association with the disease shigellosis (Croxen and Finlay, 2010). Enteroaggregative E. coli (EAEC) was first described in 1987 in a child suffering from acute diarrhoea in Lima, Peru (Nataro et al., 1987). Since its discovery, EAEC have been associated with persistent diarrhoea in children living in EAEC-endemic areas (Nataro et al., 1987), individuals infected with the human immunodeficiency virus (HIV) (Mathewson et al., 1995), and as a cause of diarrhoea in travellers from industrialised countries visiting the developing world. The pathogenesis of EAEC is determined by its ability to adhere to intestinal cells, produce enterotoxins and cytotoxins, and induce inflammation of the intestinal wall. EAEC are characterised by the ability to colonise either the small or large intestinal mucosa, but primarily the colon, by aggregative adhesion.
The diffusely adherent E. coli (DAEC) are considered a diarrhoeagenic class of organisms that colonise the small intestines, causing diarrhoea in children between the age of 18 months and 5 years in developing countries (Mansan-Almeida, Pereira and Giugliano, 2013). These strains are characterised by the diffuse adherence pattern on cultured epithelial cells HeLa or Hep-2 (Croxen and Finlay, 2010). DAEC strains are able to produce finger-like projections that extend from the surface of infected Caco-2 or HEp-2 cells (Cookson and Nataro, 1996). These projections supposedly “embed” the bacteria, providing some protection against gentamicin but without complete internalisation of the cell, however the role for this phenotype in pathogenesis has not yet been determined.
The enterohaemorrhagic E. coli (EHEC) pathotype was first defined in 1983 after two outbreaks of gastrointestinal illness characterised by severe abdominal cramps, watery diarrhoea which progressed to extremely bloody diarrhoea, and was not accompanied by fever (Riley et al., 1983; Karmali et al., 1983). EHEC was defined based on the serological evidence and presence of a specific cytotoxin derived from these two outbreaks. EHEC strains comprise a subgroup of the Shiga toxin-producing E. coli (STEC), which encompasses EHEC and the lesser virulent/avirulent STEC. Owing to their human pathogenicity, some STEC strains are also designated as EHEC
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(Nataro and Kaper, 1998). The major defining feature of EHEC is the production of phage- encoded Shiga toxin, Stx1 and/or Stx2, which are responsible for serious disease in humans, such as HUS and HC.
In 2011, an outbreak strain associated with haemolytic-uraemic syndrome and bloody diarrhoea in Europe, was identified as an EAEC strain that acquired the prophage-encoded Shiga toxin of EHEC, thus combining the virulence potentials of two different pathogens (Denamur, 2011). This combination of genomic features, associating characteristics from both EAEC and EHEC, gave rise to a new pathotype: the enteroaggregative-haemorrhagic E. coli (EAHEC). This outbreak highlighted the ability of E. coli to recombine and produce new combinations of genes, resulting in new lineages. The EAHEC outbreak also provided a good example of the application of modern sequencing technologies to rapidly and accurately identify causative strains, which in the past, relied heavily on low resolution methods such as serotyping of infectious organisms (Denamur, 2011).
The adherent-invasive E. coli (AIEC) are a pathotype of E. coli that have been implicated in the pathogenesis of Crohn’s disease (Darfeuille-Michaud, 2002). AIEC are unusual among intestinal
E. coli pathotypes in that they are not associated with diarrhoea. The high prevalence of
adherent E. coli isolated from the ileal mucosa of patients with Chron’s disease led to the characterisation of several strains, which failed to detect any virulence-associated genes that are traditionally present in typical pathogenic species. One characteristic of these strains is the ability to adhere to and invade intestinal epithelial cells, as well as the ability to replicate within macrophages, which discerns them from other varieties of E. coli, including commensals. These strains were therefore categorised as the specific pathogenic group known as AIEC (Darfeuille- Michaud, 2002).