Effects of the Escherichia coli Bacterial Toxin Cytotoxic Necrotizing Factor 1 on Different Human and Animal Cells: A Systematic Review

Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic Escherichia coli extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.     

克罗诺杆菌属致病性研究进展

克罗诺杆菌作为婴儿配方粉中的A类致病菌,能引起新生儿脑膜炎、坏死性小肠结肠炎和菌血症等,死亡率高达40%～80%,引起了广泛关注。本文基于国内外有关克罗诺杆菌的文献报道,从流行病学特征、血清学分型特点、环境抗性特征、毒力基因以及与致病相关的优势克隆群等方面进行了总结,提出通过增强临床监测体系,掌握该菌在我国的发病情况及高危食品,从而制定相应的防控策略。     

Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection

Ran Binding Protein 2 (RanBP2 or Nucleoporin358) is one of the main components of the cytoplasmic filaments of the nuclear pore complex. Mutations in the RANBP2 gene are associated with acute necrotizing encephalopathy type 1 (ANE1), a rare condition where patients experience a sharp rise in cytokine production in response to viral infection and undergo hyperinflammation, seizures, coma, and a high rate of mortality. Despite this, it remains unclear howRanBP2 and its ANE1-associated mutations contribute to pathology. Mounting evidence has shown that RanBP2 interacts with distinct viruses to regulate viral infection. In addition, RanBP2 may regulate innate immune response pathways. This review summarizes recent advances in our understanding of how mutations in RANBP2 contribute to ANE1 and discusses how RanBP2 interacts with distinct viruses and affects viral infection. Recent findings indicate that RanBP2 might be an important therapeutic target, not only in the suppression of ANE1-driven cytokine storms, but also to combat hyperinflammation in response to viral infections.     

Pathogenesis and Preventive Tactics of Immune-Mediated Non-Pulmonary COVID-19 in Children and Beyond

The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible.     

Necrotizing fasciitis and infective endocarditis caused by Escherichia coli in a hemodialysis patient

Patients with uremia are often immunocompromised and uremia patients undergoing maintenance dialysis are often vulnerable to uncommon infections. We report a 40‐year‐old man who was undergoing maintenance hemodialysis and was initially diagnosed with monomicrobal necrotizing fasciitis of the lower limbs, based on blood and pus cultures that yielded Escherichia coli. His condition improved after surgical debridement and antibiotic therapy. However, he eventually died of intracranial hemorrhage related to septic emboli. Concurrent infective endocarditis was diagnosed based on an echocardiogram that indicated vegetation in the left ventricular region. Escherichia coli‐related necrotizing fasciitis and infective endocarditis is rarely seen in clinical practice. There should be a high index of suspicion for multiple infections when a hemodialysis patient presents with an uncommon infection.     

Necrotizing fasciitis of thigh associated with Escherichia Coli bacteremia in a patient on chronic hemodialysis

Necrotizing fasciitis is a lethal soft tissue infection for its rapid progression to septic shock. We present a 59‐year‐old male on chronic hemodialysis (HD). We made the diagnosis of necrotizing fasciitis of the right thigh due to the crepitus from physical examination and subcutaneous emphysema from an X film. He was successfully treated with antibiotics and surgical debridement. The blood and surgical drainage cultures showed Escherichia coli, which is less commonly seen in cutaneous infection. The colonoscopic finding revealed adenomatous polyps. Necrotizing fasciitis in patients on HD requires early diagnosis and aggressive treatment to ensure the favorable clinical outcomes.     

Necrotizing Enterocolitis: Overview on In Vitro Models

Necrotizing enterocolitis (NEC) is a gut inflammatory disorder which constitutes one of the leading causes of morbidity and mortality for preterm infants. The pathophysiology of NEC is yet to be fully understood; several observational studies have led to the identification of multiple factors involved in the pathophysiology of the disease, including gut immaturity and dysbiosis of the intestinal microbiome. Given the complex interactions between microbiota, enterocytes, and immune cells, and the limited access to fetal human tissues for experimental studies, animal models have long been essential to describe NEC mechanisms. However, at present there is no animal model perfectly mimicking human NEC; furthermore, the disease mechanisms appear too complex to be studied in single-cell cultures. Thus, researchers have developed new approaches in which intestinal epithelial cells are exposed to a combination of environmental and microbial factors which can potentially trigger NEC. In addition, organoids have gained increasing attention as promising models for studying NEC development. Currently, several in vitro models have been proposed and have contributed to describe the disease in deeper detail. In this paper, we will provide an updated review of available in vitro models of NEC and an overview of current knowledge regarding its molecular underpinnings.