Escherichia coli produces polysaccharide capsules that, based on their mechanisms of synthesis and assembly, have been classified into four groups. The group 4 capsule (G4C) polysaccharide is frequently identical to that of the cognate lipopolysaccharide O side chain and has, therefore, also been termed the O-antigen capsule. The genes involved in the assembly of the group 1, 2, and 3 capsules have been described, but those required for G4C assembly remained obscure. We found that enteropathogenic E. coli (EPEC) produces G4C, and we identified an operon containing seven genes, ymcD, ymcC, ymcB, ymcA, yccZ, etp, and etk, which are required for formation of the capsule. The encoded proteins appear to constitute a polysaccharide secretion system. The G4C operon is absent from the genomes of enteroaggregative E. coli and uropathogenic E. coli. E. coli K-12 contains the G4C operon but does not express it, because of the presence of IS1 at its promoter region. In contrast, EPEC, enterohemorrhagic E. coli, and Shigella species possess an intact G4C operon.

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC, respectively) strains represent a major global health problem. Their virulence is mediated by the concerted activity of an array of virulence factors including toxins, a type III protein secretion system (TTSS), pili, and others. We previously showed that EPEC O127 forms a group 4 capsule (G4C), and in this report we show that EHEC O157 also produces a G4C, whose assembly is dependent on the etp, etk, and wzy genes. We further show that at early time points postinfection, these G4Cs appear to mask surface structures including intimin and the TTSS. This masking inhibited the attachment of EPEC and EHEC to tissue-cultured epithelial cells, diminished their capacity to induce the formation of actin pedestals, and attenuated TTSS-mediated protein translocation into host cells. Importantly, we found that Ler, a positive regulator of intimin and TTSS genes, represses the expression of the capsule-related genes, including etp and etk. Thus, the expression of TTSS and G4C is conversely regulated and capsule production is diminished upon TTSS expression. Indeed, at later time points postinfection, the diminishing capsule no longer interferes with the activities of intimin and the TTSS. Notably, by using the rabbit infant model, we found that the EHEC G4C is required for efficient colonization of the rabbit large intestine. Taken together, our results suggest that temporal expression of the capsule, which is coordinated with that of the TTSS, is required for optimal EHEC colonization of the host intestine.Enterohemorrhagic Escherichia coli (EHEC) is an emerging pathogen causing outbreaks of food-borne gastroenteritis manifested by bloody diarrhea, which may progress to the potentially fatal hemolytic-uremic syndrome. The latter involves severe complications, such as renal impairment, hypertension, and central nervous system manifestations mainly caused by SLT toxins (3,22). EHEC belongs to the family of the attaching and effacing (AE)-inducing pathogens, which includes the closely related species enteropathogenic E. coli (EPEC), Citrobacter rodentium, and rabbit EPEC. When colonizing the gut, these pathogens form AE lesions on the intestinal epithelial cell surface. AE lesions are characterized by localized destruction of the brush border microvilli, intimate bacterial attachment to host cells, and the formation of actin structures, termed pedestals, beneath the attached bacteria (24). This histopathology is dependent upon a type III protein secretion system (TTSS), which functions as a molecular syringe to translocate effector proteins from the bacterial cytoplasm directly into the cytoplasm of host epithelial cells (15). These effectors subvert normal host cell functions and are required for efficient host colonization (15,34,35). One of these effectors, Tir, is inserted into the host cell membrane to form a binding site for an outer membrane adhesin, intimin. Interaction of intimin with translocated Tir promotes tight bacterial attachment to the ho...

Cogan's syndrome (CS) is a rare chronic inflammatory disorder, classically characterized by interstitial keratitis and sensorineural hearing loss. Recurrent episodes of inner ear disease might result in deafness. In some patients, it may also be accompanied by systemic vasculitis. Diagnosis of CS is often missed or delayed due to its rarity, the nonspecific clinical signs at onset, and the lack of a confirmatory diagnostic test. The mechanisms responsible for CS are unknown; however, in the last decade, the pathogenesis has been somewhat elucidated, suggesting that the disease is a result of inner ear autoimmunity. The autoimmune hypothesis postulates the triggering of the disease by a viral infection via a number of mechanisms, which are mainly as follows: antigenic mimicry, self-perpetuating inflammation by cytokine release, and unveiling hidden epitopes. Aside from its clinical resemblance to other autoimmune disorders, some autoantigen has apparently been identified, namely, CD148 and connexine 26. Treatment should begin as early as possible. While treatment is based primarily on glucocorticoids, there is no standard alternative for patients who respond poorly. Failure of conventional treatment could lead to profound sensorineural hearing loss. From the limited data we have, infliximab seems to be the most promising biological remedy, enabling steroid tapering and leading to improvement in auditory/ocular disease, with better results when administered in early stages. Proposed guidelines for the use of infliximab in CS are found in the last table of the review, in an attempt to define the proper timing for initiating infliximab treatment in order to avoid permanent disability.

On the basis of 6 RCT's (n = 242), there is evidence to support the effectiveness of intratympanic steroids and gentamicin to control symptoms of vertigo in MS/D albeit with a risk of hearing loss with gentamicin. However, there was no consensus found on doses or treatment protocols. There was no evidence to support the use of other forms of intratympanic therapy (antivirals and latanoprost) in MS/D.

Clinicians should be aware of this distinct form of foreign body aspiration, its method of diagnosis, and extraction techniques. A cultural investigation showed a difference in the turban-fastening technique of young girls as compared with their mothers. Removal by rigid bronchoscopy is a safe method with a high success rate and should be considered as the preferred extraction method of choice.

Given that the primary surgery for the VS was only for tumours that were relatively large or grew during conservative treatment, the low rate of tumour remnant growth (7%) is reassuring. It may be appropriate to have a lower threshold for leaving tumour on the facial nerve in non-NF2 patients where complete resection may jeopardise facial nerve function.

This study did not demonstrate association between vestibular physical examination, vestibular questionnaires, and ENG results. Although history (augmented by questionnaires) and physical examination are the initial steps in the evaluation of vertigo, the current study suggests that they should be complemented by objective testing for evaluation of inner ear origin of vertigo.

The initial events of viral infection at the primary mucosal entry site following horizontal person-to-person transmission have remained ill defined. Our limited understanding is further underscored by the absence of animal models in the case of human-restricted viruses, such as human cytomegalovirus (HCMV) – a leading cause of congenital infection and a major pathogen in immunocompromised individuals. Here we established a novel ex vivo model of HCMV infection in native human nasal turbinate tissues. Nasal-turbinate tissue viability and physiological functionality were preserved for at least seven days in culture. We found that nasal mucosal tissues were susceptible to HCMV infection, with predominant infection of ciliated respiratory epithelial cells. A limited viral spread was demonstrated, involving mainly stromal- and vascular endothelial cells within the tissue. Importantly, functional antiviral and pro-leukocyte-chemotactic signaling pathways were significantly upregulated in the nasal mucosa in response to infection. Conversely, HCMV downregulated the expression of nasal epithelial-cell related genes. We further revealed tissue-specific innate immune response patterns to HCMV, comparing infected human nasal-mucosal and placental tissues, representing the viral entry- and the maternal-to-fetal transmission site, respectively. Taken together, our studies provide insights into the earliest stages of HCMV infection. Studies in this model could help evaluate new interventions against the horizontal transmission of HCMV. IMPORTANCE HCMV is a ubiquitous human pathogen, causing neurodevelopmental disabilities in congenitally infected children and severe disease in immunocompromised patients. The earliest stages of HCMV infection in the human host have remained elusive in the absence of a model for the viral entry site. Here we describe the establishment and use of a novel nasal turbinate organ culture, to study the initial steps of viral infection and the consequent innate immune responses, within the natural complexity and the full cellular repertoire of human nasal mucosal tissues. This model can be applied to examine new antiviral interventions against the horizontal transmission of HCMV and potentially other viruses.