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Mucosal interactions with enteropathogenic bacteria
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Nadine Cerf-Bensussan, Pamela Schnupf, Valérie Gaboriau-Routhiau, Philippe J. Sansonetti
A distinct original adhesion pathway has been developed by EPEC and EHEC strains that induce the characteristic “attaching and effacing” epithelial lesions. After intimate attachment to intestinal epithelial cells via their adhesins and bundle-forming pili, these bacteria use their type III secretion system (T3SS) to rapidly translocate a protein called Tir (for translocated intimin receptor) into the cytosol of host cells (see later for T3SS description). Tir is displayed at the host-cell surface and acts as a receptor for the bacterial outer membrane protein intimin, resulting in Tir clustering and initiation of the cytoskeleton rearrangements that lead to attaching and effacing lesions (Figure 25.3).
Engineering Escherichia coli to Combat Cancer
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Carlos Piñero-Lambea, David Ruano-Gallego, Gustavo Bodelón, Beatriz Álvarez, Luis Ángel Fernández
Inspired by the modular organization of the natural E. coli intimin family of non-fimbrial adhesins (Fig. 7.1A), we developed synthetic adhesins (SAs) capable of mediating specific adhesion of engineered E. coli cells to target cells and tumors in vitro and in vivo [38]. SAs consist in the highly stable β-barrel module derived from an N-terminal fragment of intimin (Int) called Neae (residues 1-654) that tethers the polypeptide in the OM and allows the display on the bacterial surface of a single antibody variable domain (VHH) of high affinity and specificity (Fig. 7.1A). VHHs, also referred to as nanobodies (Nbs), are small antibody fragments comprising a single variable domain from the heavy chain-only antibodies of camelids (e.g., dromedaries and llamas) [60, 61]. Nbs have a number of properties that make them attractive antibody molecules, such as their small size (ca. 14 kDa), simple structure, high affinity and specificity, distinct epitope recognition, high stability, and similarity to human VH sequences.
Escherichia
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
EHEC is characterized by the production of Shiga toxins (Stx1 and/or Stx2, leading to its alternative name of STEC) and the formation of A/E lesion, notably in the cecum and ascending colon [14–16]. EHEC typically causes an afebrile bloody colitis (bloody stools with ulcerations of the bowel) known as hemorrhagic colitis (HC), which is characterized by the sudden onset of abdominal pain, severe cramps, and diarrhea within 24 h. In about 10% of patients (e.g., children and the elderly), infection with EHEC O157 may result in HUS, which is defined by acute renal failure, hemolytic anemia, and thrombocytopenia. Colonoscopy examination reveals the presence of edema, erythema (redness), hemorrhage, erosion, and, occasionally, a long ulcer-like lesion, with a marked narrowing of the luminal space. Histologic examination indicates destruction of the surface epithelium, neutrophil infiltration of the lamina propria, and the formation of crypt abscesses. In patients (especially children of <5 years of age and the elderly) with diarrhea and HUS, renal pathology consists of endothelial swelling and glomerular thrombosis with congested rather than ischemic glomeruli. The most prevalent EHEC serotype causing outbreaks in North America and other parts of the world is O157:H7 [17,18]. Besides Shiga toxin, which may account for the severe complications including HUS, O157:H7 expresses several other virulence factors including intimin, translocated intimin receptor (Tir), a T3SS, and enterohemolysin [19]. The genes encoding many of these factors are located on a 44 kb pathogenicity island (also known as the locus of enterocyte effacement or the LEE locus) [20–22]. Cattle act as a primary reservoir for EHEC, although vegetables (lettuce, spinach, and sprouts) and fruits may also serve as vehicles for EHEC outbreaks [23].
2-deoxy-D-glucose mitigates Citrobacter rodentium and dibenzazepine-induced gastrointestinal damage and colitis: novel implications of 2-DG polypharmacopea
Published in International Journal of Radiation Biology, 2023
Ishfaq Ahmed, Amit Verma, Shahid Umar, Rao V. L. Papineni
The mice were inoculated orally with a 16-h culture of C. rodentium (biotype 4280, ATCC, 108 CFUs) identified as pink colonies on MacConkey agar to induce Transmissible Murine Colonic Hyperplasia (TMCH) (Ahmed et al. 2012; Ahmed et al. 2018; Ahmed et al. 2020). C. rodentium biotype 4280 is a unique mouse-specific strain induce histopathological changes known as attaching and effacing lesions (Barthold et al. 1977), this is by adhering to the mature surface colonocytes within the distal colon. RT-PCR for bacterial intimin in whole tissue extracts was used to assay the adherent bacteria (Umar et al. 2003). Age- and sex-matched control mice received only the sterile culture medium. A cell-permeable inhibitor of γ-secretase, Dibenzazepine (DBZ) (EMD Chemicals, Inc., Gibbstown, USA) was used to block Notch signaling in vivo (Milano et al. 2004; Ahmed et al. 2012; Ahmed et al. 2018). DBZ was prepared by suspending in 0.5% (w/v) HPMC and 0.1% (w/v) Tween-80 in water and then given to mice intraperitoneally (at 10 μmol/kg body weight) for 10 consecutive days starting two days post-CR infection. 2-DG was fed in daily drinking water with free access with 2-DG containing 0.4% 2-DG (w/v) (Singh et al. 2015). A combination of two antibiotics 1 g/l metronidazole and 0.2 g/l ciprofloxacin (Wako) was given to the mice in drinking water 2 days post CR-infection for 10 days to deplete microbiota.
β-arrestin 2 quenches TLR signaling to facilitate the immune evasion of EPEC
Published in Gut Microbes, 2020
Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Yu Wang, Shichao Huang, Ningning Liu, Chunmei Xia, Nissan Yissachar, Feng Huang, Yiwei Chu, Dapeng Yan
Enteropathogenic Escherichia coli (EPEC) belongs to a group of pathogenic organisms that adhere to the intestinal epithelial cell surface to form an attaching and effacing lesion.1,2 It continues to be a significant cause of infantile diarrhea in developing countries and contributes to high morbidity and mortality.3-5 Translocated intimin receptor (Tir) is one of the most important virulence factors that is essential for disease development.6,7 Tir is injected into host cells by a type III secretion system (T3SS) and spans the host cell membrane with its amino and carboxyl termini in the host cytoplasm. The central extracellular domain of Tir is engaged by the bacterial surface ligand intimin, which mediates intimate adhesion of the bacteria to host cells.8 Intimin-dependent clustering of Tir triggers the host protein N-WASP to form the Arp2/3 complex, leading to host cytoskeleton rearrangement to form pedestals, which promotes bacterial colonization and infection.9,10 Besides its role in actin rearrangement, Tir shares sequence similarity with cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs), which play an inhibitory role and promote immune evasion of EPEC.11 However, the underlying molecular mechanism by which Tir regulates immune inhibition remains elusive.
Epidemiology of Shiga toxin-producing Escherichia coli O157:H7 in Africa in review
Published in Southern African Journal of Infectious Diseases, 2018
STEC O157:H7 possesses different virulence factors that are important in pathogenicity. The major virulence factor is the shiga toxin. Two forms of the toxin, stx1 and stx2 encoded by stx1 and stx2 genes are known59 and reported to be responsible for haemorrhagic uremic syndrome (HUS).60 The stx1 is divided into three subtypes (stx1a, stx1c and stx1d) while seven subtypes form the stx2 group (stx2a, stx2b, stx2c, stx2d, stx2e, stx2f and stx2g).61 Of the two groups, subtypes of stx2 are associated with more severe HUS syndrome.62 Shiga toxins, which are protein molecules, bind to eukaryotic surface cells and inhibit protein synthesis with the death of host cells as a consequence.63 Intimin is another virulence factor which is coded by attaching and effacing the eae gene.64 Intimin is reported to facilitate attachment of bacteria to intestinal epithelia during colonisation resulting into production of lesions and diarrhoea.59,65,66 This virulence factor is also possessed by enteropathogenic E. coli (EPEC).67 Enterohaemolysin is another virulence factor for STEC O157:H7. This protein toxin damages cell membranes of erythrocytes and is used as a surrogate tool in detection of shiga toxin-producing E. coli.68–70 Although enterohaemolysin activity can easily be visualised on blood agar cultures, confirmation is usually achieved by PCR amplification of the ehxA gene.59,68 Some other E. coli strains such as O26, O103, O111, O118, O128, O121, O45 and O145 can produce disease syndromes and have been reported to be enterohaemolysin-positive and produce shiga toxins.68,70–72 The synergic effects of these virulence factors make STEC O157:H7 a potential pathogen to humans. All virulence genes, namely stx1, stx2, eae and ehxA genes, have been detected in humans, livestock, food products and the environment in eight different combinations as reported in 22 studies from Africa.8 The most dominant combination was stx1+stx2. Cattle are the most common source of STEC O157:H7, as shown in Table 2. Therefore, it is important to consider the use of diagnostic approaches which target different genes so as to increase the sensitivity of STEC O157:H7-related studies.