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Major achievements in the understanding of thrombotic microangiopathies (TMA) have not only resulted in a reclassification of TMA but most of all they have culminated in the design of new treatments and have enabled clinicians to better delineate their prognosis. Recent multicenter studies have improved our understanding of the prognosis of atypical hemolytic and uremic syndromes (aHUS). More specifically, they have highlighted the role of genetic testing on predicting the recurrence of aHUS, the risk of chronic kidney disease and the recurrence following kidney transplantation. A major advance consisted of the identification of the alternative complement pathway in the pathogenesis of aHUS, thus paving the way for the use of the C5a inhibitor eculizumab in this indication. Eculizumab has thereafter dramatically improved the management of patients affected with aHUS. During spring 2011, a great epidemic of entero-hemorrhagic Escherichia coli (EHEC) associated HUS occurred in Germany, providing clinicians the opportunity to examine the relevance of antibiotic prophylaxis, plasma exchange and eculizumab in EHEC-associated HUS. In this work, we herein present advances achieved in the setting of therapeutic management and prognosis in HUS and other related TMA syndromes., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Annually, there are 165 million cases of shigellosis resulting in 1.1 million deaths in the developing world. Two species of the causative agent, Shigella dysenteriae 1 and Shigella flexneri, are responsible for acute diarrheal illness. Vaccines are being developed against both but many questions remain about the disease burden, distribution of species in space and time, and community-level risk factors. This study answers two questions. What are the differences in neighborhood-level risk factors between S. dysenteriae 1 and S. flexneri? Does shigellosis caused by the two different species occur in the same neighborhoods and are those high-risk neighborhoods persistent in time? Cases from a hospital in rural Bangladesh were assigned to one of the two shigellosis types and age-matched individuals were randomly chosen from the community to be controls. Information was collected for neighborhood-level variables hypothesized to be related to shigellosis. During the 3-year study period, there were 161 cases of S. dysenteriae 1 and 225 cases of S. flexneri. Incidence of both types was highest in children under 2 followed by children from 2 to 5. The location of S. dysenteriae 1 risk varies in time but S. flexneri risk areas were persistent in time. Neighborhoods near bazaars with many non-septic latrines were at highest risk for S. dysenteriae 1. S. flexneri was most common in flood-controlled areas. S. dysenteriae 1 risk is more related to hygiene and sanitation and S. flexneri is more related to the environment.

A Schiff base complex of chromium(III), transdiaqua[N,N'ethylenebis (salicylideneimine)chromium(III)]perchlorate, [Cr(salen)(OH(2))(2)](+), was found to have an inhibitory effect on the growth of Shigella dysenteriae. The chromium(III) complex was found to cure (remove) the invasive plasmid and thereby render the microbe more sensitive to the tested antibiotics. The loss in the catalytic activity of the isolated endo-alpha-N-acetyl galactosaminidase on mucin as a substrate was also observed in the presence of [Cr(salen)(OH(2))(2)](+). This suggests that [Cr(salen)(OH(2))(2)](+) is toxic to the microbe and could make the microbe non-pathogenic and non-invasive, thus establishing its role in microbiological applications to reduce the toxic potentials of a microbe.

The ability of Shigella dysenteriae to utilize heme as an iron source is dependent on the iron-regulated expression of a number of genes including the outermembrane receptor ShuA and the cytoplasmic protein ShuS. The ShuS protein has no sequence homology with any proteins of known function and its role in heme acquisition has not been determined. In this paper we describe the purification and characterization of ShuS. The soluble oligomeric protein (650 kDa) is composed of a single type of subunit with a molecular mass of 37 kDa and binds one heme per monomer (Kd = 13 microM). In addition, the ShuS protein was shown to nonspecifically bind double-stranded DNA. It appears, therefore, that ShuS may function as both a heme storage protein, during periods of active heme transport, and as a DNA binding protein to protect the DNA from any ensuing heme mediated oxidative damage.

The main feature of virulent strains of Shigella is their ability to invade eucaryotic cells. This phenotype is both plasmid-mediated and temperature-regulated. In the present report, we demonstrate a plasmid-mediated and temperature-regulated haemolytic activity in S. flexneri, S. dysenteriae and S. sonnei. Detection of this haemolytic activity requires centrifugation of suspensions containing bacteria and erythrocytes, followed by incubation of the pellets at 37 degrees C. No soluble intra- or extracellular haemolytic activity could be detected. Dose-effect and electron microscopic studies demonstrated that direct contact of several virulent bacteria per erythrocyte was critical for haemolysis to occur. However, no local morphological alteration of the erythrocyte membrane at the site of contact with bacteria could be detected. Intensity of this haemolytic activity was fully correlated with the efficiency of penetration within HeLa cells, suggesting a common mechanism for induction of phagocytosis and lysis of erythrocytes.

Shigellae and dysentery-like Escherichia coli must invade the epithelium of the colon to cause disease which can present as dysentery, diarrhea, or both. This paper addresses the possible role of a Shigella dysenteriae-like (Shiga-like) toxin in the pathogenesis of shigellosis and E. coli diarrheal diseases. The possibility for such a role is suggested by the following observations: 1) diarrhea, considered to be a result of secretion of water by the small bowel, is frequently observed in shigellosis, a large bowel disease. 2) Even though shigellae do not invade the jejunum of monkeys fed Shigella flexneri, jejunal secretion is seen in animals with diarrhea. 3) The Shiga toxin of S. dysenteriae has enterotoxic activity and other serotypes of shigellae produce Shiga-like toxins. 4) E. coli 015 RDEC-1 causes a diarrheal disease and frequently death in young rabbits. This organism neither produces E. coli enterotoxins nor is it invasive, but it may produce low levels of a Shiga-like toxin.