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Klebsiella pneumoniae is an opportunistic pathogen that can produce moderate and severe infections in immunosuppressed hosts. In recent years, an increase in the isolation of hypermucoviscous carbapenem-resistant K. pneumoniae with sequence type 25 (ST25) in hospitals in Norwest Argentina was observed. This work aimed to study the virulence and inflammatory potential of two K. pneumoniae ST25 strains (LABACER01 and LABACER27) in the intestinal mucosa. The human intestinal Caco-2 cells were infected with the K. pneumoniae ST25 strains, and their adhesion and invasion rates and changes in the expression of tight junction and inflammatory factors genes were evaluated. ST25 strains were able to adhere and invade Caco-2 cells, reducing their viability. Furthermore, both strains reduced the expression of tight junction proteins (occludin, ZO-1, and claudin-5), altered permeability, and increased the expression of TGF-β and TLL1 and the inflammatory factors (COX-2, iNOS, MCP-1, IL-6, IL-8, and TNF-α) in Caco-2 cells. The inflammatory response induced by LABACER01 and LABACER27 was significantly lower than the one produced by LPS or other intestinal pathogens, including K. pneumoniae NTUH-K2044. No differences in virulence and inflammatory potential were found between LABACER01 and LABACER27. In line with these findings, no major differences between the strains were found when the comparative genomic analysis of virulence factors associated with intestinal infection/colonization was performed. This work is the first to demonstrate that hypermucoviscous carbapenem-resistant K. pneumoniae ST25 infects human intestinal epithelial cells and induces moderate inflammation.

ObjectivesTo estimate, overall and by organism, the incidence of infectious intestinal disease (IID) in the community, presenting to general practice (GP) and reported to national surveillance.DesignProspective, community cohort study and prospective study of GP presentation conducted between April 2008 and August 2009.SettingEighty-eight GPs across the UK recruited from the Medical Research Council General Practice Research Framework and the Primary Care Research Networks.Participants6836 participants registered with the 88 participating practices in the community study; 991 patients with UK-acquired IID presenting to one of 37 practices taking part in the GP presentation study.Main outcome measuresIID rates in the community, presenting to GP and reported to national surveillance, overall and by organism; annual IID cases and GP consultations by organism.ResultsThe overall rate of IID in the community was 274 cases per 1000 person-years (95% CI 254 to 296); the rate of GP consultations was 17.7 per 1000 person-years (95% CI 14.4 to 21.8). There were 147 community cases and 10 GP consultations for every case reported to national surveillance. Norovirus was the most common organism, with incidence rates of 47 community cases per 1000 person-years and 2.1 GP consultations per 1000 person-years. Campylobacter was the most common bacterial pathogen, with a rate of 9.3 cases per 1000 person-years in the community, and 1.3 GP consultations per 1000 person-years. We estimate that there are up to 17 million sporadic, community cases of IID and 1 million GP consultations annually in the UK. Of these, norovirus accounts for 3 million cases and 130 000 GP consultations, and Campylobacter is responsible for 500 000 cases and 80 000 GP consultations.ConclusionsIID poses a substantial community and healthcare burden in the UK. Control efforts must focus particularly on reducing the burden due to Campylobacter and enteric viruses.

The mucus layer coating the gastrointestinal tract is the front line of innate host defense, largely because of the secretory products of intestinal goblet cells. Goblet cells synthesize secretory mucin glycoproteins ( MUC2 ) and bioactive molecules such as epithelial membrane-bound mucins ( MUC1, MUC3, MUC17 ), trefoil factor peptides (TFF), resistin-like molecule β (RELMβ), and Fc-γ binding protein (Fcgbp). The MUC2 mucin protein forms trimers by disulfide bonding in cysteine-rich amino terminal von Willebrand factor (vWF) domains, coupled with crosslinking provided by TFF and Fcgbp proteins with MUC2 vWF domains, resulting in a highly viscous extracellular layer. Colonization by commensal intestinal microbiota is limited to an outer “loose” mucus layer, and interacts with the diverse oligosaccharides of mucin glycoproteins, whereas an “inner” adherent mucus layer is largely devoid of bacteria. Defective mucus layers resulting from lack of MUC2 mucin, mutated Muc2 mucin vWF domains, or from deletion of core mucin glycosyltransferase enzymes in mice result in increased bacterial adhesion to the surface epithelium, increased intestinal permeability, and enhanced susceptibility to colitis caused by dextran sodium sulfate. Changes in mucin gene expression and mucin glycan structures occur in cancers of the intestine, contributing to diverse biologic properties involved in the development and progression of cancer. Further research is needed on identification and functional significance of various components of mucus layers and the complex interactions among mucus layers, microbiota, epithelial cells, and the underlying innate and adaptive immunity. Further elucidation of the regulatory mechanisms involved in mucin changes in cancer and inflammation may lead to the development of novel therapeutic approaches.

Non-typhoidal Salmonella (NTS) is a common pathogen causing foodborne infections, bacteraemia, and extra-intestinal focal infections (EFIs) in humans. The study compares the clinical characteristics of elderly patients with NTS bacteraemia with those of young adults. Of 272 adults with NTS bacteraemia identified in this study, 162 (59·6%) were aged ⩾55 years. EFIs were observed in 36% of the 162 patients. The most common EFIs in the elderly patients (⩾55 years) was mycotic aneurysm, followed by pulmonary infections and bone/joint infections. Elderly patients more often had chronic heart, lung, renal and malignant diseases, had more EFIs, and a higher 30-day mortality rate. Independent factors of 30-day mortality in elderly patients were solid-organ tumour [adjusted odds ratio (aOR) 4·4, P=0·003], mycotic aneurysm (aOR 3·7, P=0·023) and shock (aOR 12·1, P<0·0001). HIV infection, autoimmune diseases, and receipt of immunosuppressive therapy were more often observed in young patients.

Although extraintestinal pathogenic (ExPEC) are designated by their isolation site and grouped based on the type of host and the disease they cause, most diarrheagenic (DEC) are subdivided into several pathotypes based on the presence of specific virulence traits directly related to disease development. This scenario of a well-categorized collapsed after the German outbreak of 2011, caused by one strain bearing the virulence factors of two different DEC pathotypes (enteroaggregative and Shiga toxin-producing ). Since the outbreak, many studies have shown that this phenomenon is more frequent than previously realized. Therefore, the terms hybrid- and hetero-pathogenic have been coined to describe new combinations of virulence factors among the classic pathotypes. In this review, we provide an overview of these classifications and highlight the genomic plasticity that results in some mixed pathotypes displaying novel pathogenic strategies, which lead to a new symptomatology related to diseases. In addition, as the capacity for genome interrogation has grown in the last few years, it is clear that genes encoding some virulence factors, such as Shiga toxin, are found among different pathotypes to which they have not traditionally been associated, perhaps foreshowing their emergence in new and severe outbreaks caused by such hybrid strains. Therefore, further studies regarding hetero-pathogenic and hybrid-pathogenic isolates are necessary to better understand and control the spread of these pathogens.

The purpose of this study is to examine the variations between extra-intestinal and intestinal infections of in terms of strain types, risk factors, drug susceptibility results, and the distribution of drug resistance and virulence genes. A total of 188 strains were identified to the species level using housekeeping genes ( , and ). The risk factors for extra-intestinal and intestinal infection, as well as mortality, were retrospectively examined in this study. The broth microdilution method was used to investigate the antimicrobial susceptibility profiles. Touchdown polymerase chain reaction (PCR) assays and DNA sequencing were employed to confirm virulence and the presence of drug resistance genes. The housekeeping genes identified 188 strains into 7 species. Extra-intestinal isolates generally contained and , while intestinal were (p=0.0001). Extra-intestinal infections (158/188) were the main type and accounted for 24/27 of all fatalities. Malignant tumors, hepatobiliary diseases, anemia, and hypoproteinemia were linked to infections. Poor results were associated with septic shock. Using the broth microdilution method, over 80% isolates were susceptible to most antimicrobials, except for ceftazidime (79.8%) and ceftriaxone (69.7%). Except for imipenem, intestinal strains were more susceptible to other medications than extra-intestinal. Using touch-down polymerase chain reaction testing and DNA sequencing, 6 strains, 31 strains, and a strain only had , , and , respectively. Two each possessed + , and + + + ; two each possessed + + + , and + . Thirty-four of the 42 strains mentioned above were isolated from extra-intestinal. , and , were in intestinal more frequently, but , and were in extra-intestinal more frequently. inside and outside intestinal differed in their clinical characteristics, drug susceptibility, drug resistance and virulence genes.

The intestinal mucosa is constantly exposed to commensal microbes, opportunistic pathogens, toxins, luminal components and other environmental stimuli. The intestinal mucosa consists of multiple differentiated cellular and extracellular components that form a critical barrier, but is also equipped for efficient absorption of nutrients. Combination of genetic susceptibility and environmental factors are known as critical components involved in the pathogenesis of intestinal diseases. The innate immune system plays a critical role in the recognition and elimination of potential threats by detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This host defense is facilitated by pattern recognition receptors (PRRs), in which the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has gained attention due to its role in sensing host and foreign double-stranded DNA (dsDNA) as well as cyclic dinucleotides (CDNs) produced by bacteria. Upon binding with dsDNA, cGAS converts ATP and GTP to cyclic GMP-AMP (cGAMP), which binds to STING and activates TANK binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), inducing type I interferon (IFN) and nuclear factor kappa B (NF-κB)-mediated pro-inflammatory cytokines, which have diverse effects on innate and adaptive immune cells and intestinal epithelial cells (IECs). However, opposite perspectives exist regarding the role of the cGAS-STING pathway in different intestinal diseases. Activation of cGAS-STING signaling is associated with worse clinical outcomes in inflammation-associated diseases, while it also plays a critical role in protection against tumorigenesis and certain infections. Therefore, understanding the context-dependent mechanisms of the cGAS-STING pathway in the physiopathology of the intestinal mucosa is crucial for developing therapeutic strategies targeting the cGAS-STING pathway. This review aims to provide insight into recent findings of the protective and detrimental roles of the cGAS-STING pathway in intestinal diseases.

Individuals in the developing world live in conditions of intense exposure to enteric pathogens due to suboptimal water and sanitation. These environmental conditions lead to alterations in intestinal structure, function, and local and systemic immune activation that are collectively referred to as environmental enteropathy (EE). This condition, although poorly defined, is likely to be exacerbated by undernutrition as well as being responsible for permanent growth deficits acquired in early childhood, vaccine failure, and loss of human potential. This article addresses the underlying theoretical and analytical frameworks informing the methodology proposed by the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study to define and quantify the burden of disease caused by EE within a multisite cohort. Additionally, we will discuss efforts to improve, standardize, and harmonize laboratory practices within the MAL-ED Network. These efforts will address current limitations in the understanding of EE and its burden on children in the developing world.

Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms are well-adapted to normal concentrations of bile acids in the gut. In contrast, physiological concentrations of the various intestinal bile acid species play an important role in the resistance to intestinal colonization by pathogens such as . Antibiotic therapy can perturb the gut microbiota and thereby impair the production of protective secondary bile acids. The most important bile acid transformation is 7α-dehydroxylation, producing deoxycholic acid (DCA) and lithocholic acid (LCA). The enzymatic pathway carrying out 7α-dehydroxylation is restricted to a narrow phylogenetic group of commensal bacteria, the best-characterized of which is . Like many other intestinal commensal species, 7-dehydroxylating bacteria are understudied . Conventional animals contain variable and uncharacterized indigenous 7α-dehydroxylating organisms that cannot be selectively removed, making controlled colonization with a specific strain in the context of an undisturbed microbiota unfeasible. In the present study, we used a recently established, standardized gnotobiotic mouse model that is stably associated with a simplified murine 12-species \"oligo-mouse microbiota\" (Oligo-MM ). It is representative of the major murine intestinal bacterial phyla, but is deficient for 7α-dehydroxylation. We find that the Oligo-MM consortium carries out bile acid deconjugation, a prerequisite for 7α-dehydroxylation, and confers no resistance to infection (CDI). Amendment of Oligo-MM with normalized the large intestinal bile acid composition by reconstituting 7α-dehydroxylation. These changes had only minor effects on the composition of the native Oligo-MM , but significantly decreased early large intestinal colonization and pathogenesis. The delayed pathogenesis of in -colonized mice was associated with breakdown of cecal microbial bile acid transformation.

Background: Aeromonas species are gram-negative rods usually isolated from the gastrointestinal tract. They have been occasionally reported as a cause of extra-intestinal infections such as cellulitis, cholangitis, necrotizing fascitis, meningitis, bacteremia, or peritonitis in both immunocompetent and immunocompromised patients . Aim: To determine the role and possible pathogenesis of Aeromonas in extra-intestinal infections.Settings and Design: Retrospective analysis carried out at Kasturba Hospital Manipal, Karnataka in the months of January and February 2007. Materials and Methods: Clinical manifestations and management of eight cases of extra-intestinal infections caused by A. hydrophila , from the south Karnataka coastal region were reviewed. The isolates were identified with the help of biochemical tests using standard guidelines.Results: All patients acquired Aeromonas infections in the community. Five (62.5%) had underlying illnesses, such as liver disease, diabetes mellitus or malignancy. Five (62.5%) had polymicrobial infections, and three (37.5%) were complicated with bacteremia. These included three patients with ulcers or abscess over the lower leg, two with cellulitis due to snake bite and one each with pelvic inflammatory disease, spontaneous bacterial peritonitis and pneumonia. A. hydrophila was found to be a causative agent of pelvic inflammatory disease or cellulitis following sea snake bite, and such a clinical scenario has not been previously described. Seven patients survived the illness. Conclusions: Isolation of A. hydrophila from extra-intestinal specimens demands utmost clinical and microbiological vigilance in diagnosis, since the organism can cause serious infections among immunocompromised as well as immunocompetent individuals.