Bacterial Diarrhoea
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Bacterial Diarrhoea |
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Bacterial Diarrhoea EHEC: AD Phillips Enterohaemorrhagic Escherichia Coli and the Gut AD Phillips . Honorary Senior Lecturer & Clinical Scientist, Center for Paediatric Gastroenterology, Dept of Paediatrics & Child Health, Royal Free Hospital, London.Enterohaemorrhagic Escherichia coli (EHEC) are world-wide zoonotic pathogens [1]. In humans EHEC cause acute gastroenteritis, bloody diarrhoea and haemorrhagic colitis. Around 10% of cases develop complications, including haemolytic uraemic syndrome (HUS), with a » 5% fatality rate [1,2]. Although EHEC O157:H7 are believed to colonise the large intestine [1], EHEC attaching-effacing (A/E) lesion formation has only recently been demonstrated in man [3], with a distinct tropism for ileal Peyer’s patches. A/E activity was first associated with the EPEC eae gene encoding intimin [4]. eae is present in O157 [5] and other EHEC serogroups [6], and is necessary for colonisation in animals [7,8]. Five distinct intimin types, designated a to e are recognised [9,10], and are associated with defined EPEC and EHEC serotypes [11]. Initial adhesive events in intimin g strains appear restricted to Peyer’s patches [3,12]. A locus of enterocyte effacement [LEE] pathogenicity island, contains the genes necessary for A/E lesion in EPEC [13]. However, the O157:H7 LEE is different and cannot confer the A/E phenotype when cloned into a laboratory E coli [14]. A significant association exists between human disease isolates and the presence of eae and Shiga toxin (Stx) 2 genes [15]. Stx 1 & 2 appear to cross the intestinal epithelium via different pathways [16], without affecting barrier function, whereas the intestinal microvasculature is susceptible to toxin-mediated damage [17]. Thus, there is the possibility of ischaemic events in intestinal areas without bacterial colonisation. Stx uptake by blood neutrophils has led to the suggestion that neutrophils, by transferring toxin from intestine to kidney have an important role in HUS [18]. Antibiotic treatment in Stx-positive O157:H7 is not recommended as it appears to increase the risk of HUS [19]. The publication of the complete O157:H7 genome [20] offers a great advance in understanding this important pathogen. References: 1 Nataro, J. P. and Kaper, J. B. Diarrheagenic Escherichia coli.
Clin Microbiol Rev 1998:11:142-201. Unusual Enteric Protozoan Infections in Patients with AIDS Alan Curry . Public Health Laboratory, Withington Hospital, Manchester, M20 2LR, UK.AIDS is a worldwide problem. Many AIDS patients have symptoms of malabsoption, chronic diarrhoea and wasting. Investigations into the causes of these symptoms have revealed several previously unknown protozoan parasites or have shown that infections previously considered rare are much more common in this group of immunocompromised individuals. Microsporidia are ubiquitous in nature but were virtually unknown as causes of human disease before the advent of AIDS. Enteric infections due to these organisms are now commonly recognised. Enterocytozoon bieneusi was first described in 1985 and is the most commonest microsporidian identified in humans. A second enteric species, Encephalitozoon intestinalis was recognised in 1992. Dual infection has also been reported. A single case of enteric Encephalitozoon cuniculi infection has been reported in a patient with disseminated E. cuniculi infection, although the species infection the intestine was not specifically identified. Diagnosis can be problematical and speculation is of importance as Encephalitozoon infections are treatable, whereas E. bieneusi infection is often refractory to treatment. Possible animal sources of human infections are only just being recognised. Unrelated to the microsporidians is the coccidian Isospora belli. Once considered a rare, mainly tropical, human infection, this parasite is now more commonly diagnosed in those infected with HIV even in temperate regions. Although generally thought of as an enteric pathogen, this organism can disseminate. This presentation will review the current state of knowledge about these infections. EPEC – Molecular Intimacy Elizabeth Hartland1 and Gad Frankel2. 1Department of Microbiology, Monash University, Victoria 3800, Australia. 2Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UKEnteropathogenic Escherichia coli (EPEC) is an important cause of diarrhoea in young children and makes a major contribution to infant morbidity and mortality in the developing world. A striking feature of EPEC diarrhoea is the age-dependent susceptibility of patients. EPEC is principally a pathogen of the small bowel and one of several gastrointestinal pathogens of humans and animals able to cause distinctive lesions in the gut, termed attaching and effacing (A/E) lesions. This group of A/E pathogens also includes the closely related human pathogen, enterohaemorrhagic E. coli (EHEC). A/E lesions are characterised by localised destruction of intestinal microvilli, intimate attachment of the bacteria to the host cell surface and the formation of pedestal-like structures underneath tightly adherent bacteria. All the genes required for A/E lesion formation are present in a 35-kb pathogenicity island, termed LEE. The LEE region contains 41 open reading frames organised into several polycistronic operons. Most of the genes in LEE code for a type III secretion system that directs the secretion of several other LEE-encoded proteins, the EPEC secreted proteins or Esps. These include EspA, EspD, EspB, EspF, EspG and Tir. The LEE region also contains the eae gene, which codes for an outer membrane protein adhesin, intimin. Intimate adherence of EPEC to the host epithelial cell surface depends on a specific and well-characterised protein/protein interaction between intimin and Tir. Tir is delivered into the host cell membrane by the LEE-encoded type III secretion system, where it acts as a receptor for intimin. Role of Secretory Antibody in the Colonisation of the Gastrointestinal Tract by Normal Flora and Bacterial Pathogens TK Uren, 1 LC Sait,2 OLC Wijburg,1,2 CP Simmons,3 PH Janssen2 & RA Strugnell.1,2 . 1CRC for Vaccine Technology & 2Dept. Microbiology and Immunology, The University of Melbourne, Parkville VIC 3010 Australia. 3Dept. Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, SW7 2AZ, UK The gastrointestinal tract (GIT) is the portal of entry for many viral, bacterial and eucaryotic pathogens. The GIT is protected from pathogen entry by physical barriers (e.g. stomach acidity, mucous and peristalsis) and putative immunological barriers including mucosal lymphocytes, phagocytes and secretory antibodies. We investigated the role of murine secretory antibodies in normal flora and pathogen colonisation by using gene targeting to generate a mouse deficient in secretory antibodies. The mouse, which is mutant for the polymeric immunoglobulin receptor (pIgR-/-), lacks secretory IgA (SIgA) in faeces and gastrointestinal washings. The number and types of flora bacteria which colonise the distal ileum of pIgR-/- and control C57BL/6 mice were compared using quantitative culture. These studies revealed that, while absolute numbers within groups varied, the characteristic bacterial families and genera including enterobacteriacae and lactobacilli were present in both control and SIgA-deficient animals. The murine pathogens Salmonella enterica var Typhimurium and Citrobacter rodentium, models for human typhoid and EPEC infections respectively, were also studied in the pIgR-/- mouse. Invasion through the epithelial by S. Typhimurium was essentially similar in normal and sIgA-deficient mice, regardless of their immunisation status. Some small increases in early colonisation (i.e. 6 hours) by S. Typhimurium was observed in naïve pIgR-/- animals compared with counterpart C57BL/6 animals – this transient difference in colonisation efficiency was more marked in naïve SIgA-negative mice infected with C. rodentium. SIgA-deficient mice also carried and secreted C. rodentium for longer than normal animals. These data suggest that the presence or absence of SIgA may have little impact on the normal flora of adult mice, or in resistance to acute, highly invasive pathogens such as S. Typhimurium. Non-immune secretory antibodies however do appear to confer some early resistance to initial colonisation by mucosal apthogens, especially those which are not invasive (i.e. C. rodentium). Specific SIgA may have a role in the ultimate clearance of mucosal pathogens such as C. rodentium and, by inference, EPEC. IgA deficiency is the commonest human immunodeficiency - our studies suggest that superficial gastrointestinal infection, like some respiratory infections, may be more common in the IgA-deficient cohort and that secretory antibodies may serve to limit the development of chronic gut infections. |
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