The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.

http://cbs.cau.edu.cn/module/download/downfile.jsp?classid=0&filename=1412151020189505364.pdf

Bifidobacteria can protect from enteropathogenic infection through production of acetate

Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli.

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Background We describe an outbreak of gastroenteritis and the hemolytic–uremic syndrome caused by Shiga-toxin–producing Escherichia coli in Germany in May, June, and July, 2011. The consumption of sprouts was identified as the most likely vehicle of infection. Methods We analyzed data from reports in Germany of Shiga-toxin–producing E. coli gastro enteritis and the hemolytic–uremic syndrome and clinical information on patients presenting to Hamburg University Medical Center (HUMC). An outbreak case was defined as a reported case of the hemolytic–uremic syndrome or of gastroenteritis in a patient infected by Shiga-toxin–producing E. coli, serogroup O104 or serogroup unknown, with an onset of disease during the period from May 1 through July 4, 2011, in Germany. Results A total of 3816 cases (including 54 deaths) were reported in Germany, 845 of which (22%) involved the hemolytic–uremic syndrome. The outbreak was centered in northern Germany and peaked around May 21 to 22. Most of the patients in whom the hemolytic–uremic syndrome developed were adults (88%; median age, 42 years), and women were overrepresented (68%). The estimated median incubation period was 8 days, with a median of 5 days from the onset of diarrhea to the development of the hemolytic–uremic syndrome. Among 59 patients prospectively followed at HUMC, the hemolytic–uremic syndrome developed in 12 (20%), with no significant differences according to sex or reported initial symptoms and signs. The outbreak strain was typed as an enteroaggregative Shiga-toxin–producing E. coli O104:H4, producing extended-spectrum beta-lactamase. Conclusions In this outbreak, caused by an unusual E. coli strain, cases of the hemolytic–uremic syndrome occurred predominantly in adults, with a preponderance of cases occur ring in women. The hemolytic–uremic syndrome developed in more than 20% of the identified cases.

/pdf/epidemic-profile-of-shiga-toxin-producing-escherichia-coli-54g685gdez.pdf

Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany

The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us We define six categories of autoinflammatory disease: IL-1β activation disorders (inflammasomopathies), NF-κB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside

/pdf/horror-autoinflammaticus-the-molecular-pathophysiology-of-16vahq02rm.pdf

Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease

This review article covers the diverse pathophysiological pathways that can lead to microangiopathic hemolytic anemia and a procoagulant state with or without damage to the kidneys and other organs.

/pdf/syndromes-of-thrombotic-microangiopathy-3pa0wmv320.pdf

Syndromes of Thrombotic Microangiopathy

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71144-2.pdf

Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome

Shiga-toxin-producing and haemolytic uraemic syndrome

Hematuria is not a rare finding during adolescence. The high prevalence of microscopic hematuria is not surprising when one considers the vast number of ways in which RBC can end up in the urine. The adolescent presenting with gross hematuria, proteinuria, or microscopic hematuria in combination with other symptoms of genitourinary disease is more likely to require a therapeutic intervention than is the individual found incidentally to have microscopic hematuria. Screening for hematuria is not supported by current evidence. When it is discovered as the result of a screening examination, persistent microscopic hematuria in an otherwise asymptomatic individual may not require further investigation; however, the renal ultrasound examination has little risk and is helpful in diagnosing many of the conditions amenable to intervention. Serum studies offer little useful information in the evaluation of microscopic hematuria. Addressing isolated hematuria in a systematic, evidence-based fashion can help avoid untoward patient and parental worry and excessive health care costs, without missing treatable or progressive disease entities.

Hematuria in adolescents

Reactive oxygen species (ROS) and telomere dysfunction are both associated with aging and the development of age-related diseases. Although there is evidence for a direct relationship between ROS and telomere dysfunction as well as an independent association of oxidative stress and telomere attrition with age-related disorders, there has not been sufficient exploration of how the interaction between oxidative stress and telomere function may contribute to the pathophysiology of cardiovascular diseases (CVD). To better understand the complex relationships between oxidative stress, telomerase biology and pathophysiology, we examined the telomere biology of aortic smooth muscle cells (ASMCs) isolated from mutant mouse models of oxidative stress. We discovered that telomere lengths were significantly shorter in ASMCs isolated from superoxide dismutase 2 heterozygous (Sod2+/-) mice, which exhibit increased arterial stiffness with aging, and the observed telomere attrition occurred over time. Furthermore, the telomere erosion occurred even though telomerase activity increased. In contrast, telomeres remained stable in wild-type and superoxide dismutase 1 heterozygous (Sod1+/-) mice, which do not exhibit CVD phenotypes. The data indicate that mitochondrial oxidative stress, in particular elevated superoxide levels and decreased hydrogen peroxide levels, induces telomere erosion in the ASMCs of the Sod2+/- mice. This reduction in telomere length occurs despite an increase in telomerase activity and correlates with the onset of disease phenotype. Our results suggest that the oxidative stress caused by imbalance in mitochondrial ROS, from deficient SOD2 activity as a model for mitochondrial dysfunction results in telomere dysfunction, which may contribute to pathogenesis of CVD. 

Carrie A Gordon

Papers

Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome

Shiga-toxin-producing and haemolytic uraemic syndrome

Hematuria in adolescents

Effect of oxidative stress on telomere maintenance in aortic smooth muscle cells.