The roles of toxin A and toxin B in<i>Clostridium difficile</i>infection

Steele, Jennifer; Parry, N.; Tzipori, Saul

doi:10.4161/gmic.26855

Cited by 6 publications

(4 citation statements)

References 14 publications

(24 reference statements)

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“…These results are also compatible with and might explain the high Na concentration in the stools of C. difficile colitis patients (99, 100). Although informative, these studies do not totally support the current understanding of the pathophysiology of C. difficile colitis in which Toxin B is also currently believed to contribute to the pathophysiology (101–103). Further studies are awaited comparing the effects of C. difficile and its toxins for effects on differentiated and undifferentiated human colonoids grown as monolayers.…”

Section: Human Mini-intestines In the Study Of Intestinal Pathophysiomentioning

confidence: 68%

The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology

Hasan

et al. 2017

Annu. Rev. Physiol.

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The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow “mini-intestines” ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

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Section: Human Mini-intestines In the Study Of Intestinal Pathophysiomentioning

confidence: 68%

The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology

Hasan

et al. 2017

Annu. Rev. Physiol.

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“…While CDI primarily affects the colon, it can precipitate systemic complications [177,178] (Figure 4). Animal studies have demonstrated manifestations such as cardiopulmonary injury, ascites, organ failure, and acute respiratory distress syndrome [179,180]. In pigs and mice infected with BI/NAP1/027 spores, high toxin levels have been detected in their sera, pleural, and ascitic fluids.…”

Section: Toxemia and Extraintestinal Damage Caused By Tcda And Tcdbmentioning

confidence: 99%

Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

Pourliotopoulou,

Karampatakis,

Kachrimanidou

2024

Microorganisms

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Clostridioides difficile infection (CDI) is the leading cause of nosocomial antibiotic-associated diarrhea, and colitis, with increasing incidence and healthcare costs. Its pathogenesis is primarily driven by toxins produced by the bacterium C. difficile, Toxin A (TcdA) and Toxin B (TcdB). Certain strains produce an additional toxin, the C. difficile transferase (CDT), which further enhances the virulence and pathogenicity of C. difficile. These toxins disrupt colonic epithelial barrier integrity, and induce inflammation and cellular damage, leading to CDI symptoms. Significant progress has been made in the past decade in elucidating the molecular mechanisms of TcdA, TcdB, and CDT, which provide insights into the management of CDI and the future development of novel treatment strategies based on anti-toxin therapies. While antibiotics are common treatments, high recurrence rates necessitate alternative therapies. Bezlotoxumab, targeting TcdB, is the only available anti-toxin, yet limitations persist, prompting ongoing research. This review highlights the current knowledge of the structure and mechanism of action of C. difficile toxins and their role in disease. By comprehensively describing the toxin-mediated mechanisms, this review provides insights for the future development of novel treatment strategies and the management of CDI.

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“…Clostridium difficile -важливий збудник, що викликає діарею насамперед у новонароджених поросят. Найчастіше це захворювання виникає у поросят віком 1-7 днів (Songer et al, 2000;Steele et al, 2010;Steele et al, 2014). Патогенез діареї, що асоціюється з C. difficile, в основному опосередковується дією токсину A (TcdA) і токсину B (TcdB) Kuehne et al, 2010;Steele et al, 2014).…”

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“…Найчастіше це захворювання виникає у поросят віком 1-7 днів (Songer et al, 2000;Steele et al, 2010;Steele et al, 2014). Патогенез діареї, що асоціюється з C. difficile, в основному опосередковується дією токсину A (TcdA) і токсину B (TcdB) Kuehne et al, 2010;Steele et al, 2014). І TcdA, і TcdB руйнують цитоскелет актину в уражених токсинами клітинах, що призводить до порушення важливих клітинних функцій і, у кінцевому рахунку, до їх дезорганізації та загибелі (Janoir, 2015).…”

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Bacterial Intestinal Infections of Swine

Stetsko

2022

SCIVP

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Bacterial intestinal infections are one of the main diseases in pigs of different ages. Bacterial diseases of the pig digestive tract lead to significant economic losses due to high mortality, reduced growth, treatment and prevention costs. The main bacterial intestinal infections of pigs are anaerobic enterotoxemia (clostridiosis), colibacillosis, intestinal salmonellosis, dysentery, proliferative enteropathy (ileitis). Anaerobic enterotoxemia of pigs is an acute toxic-infectious disease mainly of newborn piglets, caused by pathogenic bacteria of the genus Clostridium and characterized by hemorrhagic-necrotic inflammation of the intestinal mucosa, diarrhea and toxicosis. Swine colibacillosis is an intestinal infection caused by the enterotoxigenic Escherichia coli, which is able to produce enterotoxins that locally affect the intestines of pigs, causing diarrheal syndrome. Intestinal salmonellosis is a factorial infection. The causative agents are enteropathogenic salmonella (mainly Salmonella enterica serotype typhimurium), which cause inflammation and necrosis of the small and large intestine, leading to diarrhea, which may be accompanied by generalized sepsis. Dysentery is a severe enteroinfection of pigs caused by the anaerobic bacterium Brachyspira hyodysenteriae, characterized by fever, debilitating mucohemorrhagic diarrhea and dehydration, leading to high mortality among animals. Proliferative enteropathy is a sporadic disease of pigs caused by Lawsonia intracellularis. The acute form of ileitis, known as proliferative hemorrhagic enteritis, is characterized by intestinal hemorrhage and sudden death, and usually occurs in pigs older than 4 months. Diarrhea in piglets can also be caused by enterococci (Enterococcus spp.) and chlamydia (Chlamydia suis). Enterococcal bacteria cause diarrhea in newborn piglets, and intestinal chlamydia infections are mostly common in rearing piglets, and it is believed that most intestinal infections caused by chlamydia are subclinical. The literature review regarding the etiology, pathogenesis and clinical diagnosis of major bacterial intestinal infections in pigs is presented in the article.

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The roles of toxin A and toxin B inClostridium difficileinfection

Cited by 6 publications

References 14 publications

The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology

The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology

Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

Bacterial Intestinal Infections of Swine

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