From Nursery to Nursing Home: Emerging Concepts in Clostridioides difficile Pathogenesis

Smith, Alexander B.; Ocaña, Joshua Soto; Zackular, Joseph P.

doi:10.1128/iai.00934-19

Cited by 13 publications

(10 citation statements)

References 126 publications

(145 reference statements)

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“…TcdA and TcdB cause actin cytoskeleton disaggregation, caspases activation, and intestinal cell damage by inactivation of Rho family GTPases (Rho, Rac and Cdc42) ( 46 , 47 ). CDI spectrum varies from asymptomatic carriage, mild and moderate diarrhea to pseudomembranous colitis, severe fulminant colitis, toxic megacolon, and death, particularly in elderly patients ( 48 , 49 ).…”

Section: Vs Covid-19: Comparison Of Clinical Manifestationsmentioning

confidence: 99%

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How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

et al. 2021

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Coronavirus disease 2019 (COVID-19) has rapidly spread all over the world with a very high rate of mortality. Different symptoms developed by COVID-19 infection and its impacts on various organs of the human body have highlighted the importance of both coinfections and superinfections with other pathogens. The gastrointestinal (GI) tract is vulnerable to infection with COVID-19 and can be exploited as an alternative transmission route and target for virus entry and pathogenesis. The GI manifestations of COVID-19 disease are associated with severe disease outcomes and death in all age groups, in particular, elderly patients. Empiric antibiotic treatments for microbial infections in hospitalized patients with COVID-19 in addition to experimental antiviral and immunomodulatory drugs may increase the risk of antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI). Alterations of gut microbiota are associated with depletion of beneficial commensals and enrichment of opportunistic pathogens such as C. difficile. Hence, the main purpose of this review is to explain the likely risk factors contributing to higher incidence of CDI in patients with COVID-19. In addition to lung involvement, common symptoms observed in COVID-19 and CDI such as diarrhea, highlight the significance of bacterial infections in COVID-19 patients. In particular, hospitalized elderly patients who are receiving antibiotics might be more prone to CDI. Indeed, widespread use of broad-spectrum antibiotics such as clindamycin, cephalosporins, penicillin, and fluoroquinolones can affect the composition and function of the gut microbiota of patients with COVID-19, leading to reduced colonization resistance capacity against opportunistic pathogens such as C. difficile, and subsequently develop CDI. Moreover, patients with CDI possibly may have facilitated the persistence of SARS-CoV-2 viral particles in their feces for approximately one month, even though the nasopharyngeal test turned negative. This coinfection may increase the potential transmissibility of both SARS-CoV-2 and C. difficile by fecal materials. Also, CDI can complicate the outcome of COVID-19 patients, especially in the presence of comorbidities or for those patients with prior exposure to the healthcare setting. Finally, physicians should remain vigilant for possible SARS-CoV-2 and CDI coinfection during the ongoing COVID-19 pandemic and the excessive use of antimicrobials and biocides.

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Section: Vs Covid-19: Comparison Of Clinical Manifestationsmentioning

confidence: 99%

“…Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, celecoxib, and indomethacin are widely used for mitigation of pain, inflammation, and fever (48,(66)(67)(68). At the early stages of COVID-19, consumption of NSAIDs can help to reduce the fever as the most common symptom of the infected patients.…”

Section: Consumption Of Nsaidsmentioning

confidence: 99%

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

et al. 2021

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“…Another example of a gastrointestinal infectious disease includes Clostridioides difficile infection (CDI). C. difficile is a spore-forming pathogen that might colonize the gut of patients treated by broad-spectrum antibiotics [ 101 , 102 ]. CDI includes a broad range of disorders ranging from diarrhea to colitis and toxic megacolon [ 101 ].…”

Section: Therapeutic Relevance On Bsh-active Bacteriamentioning

confidence: 99%

“…Their incidence, severity, and costs are in continuous increase. In addition, they have evolved as a significant cause of mortality during the past decade [ 101 , 103 , 104 ]. Upon germination, vegetative cells are generated from spores, and the bacterium produces toxins that result in tissues damage, inflammation, and diarrhea [ 105 , 106 ].…”

Section: Therapeutic Relevance On Bsh-active Bacteriamentioning

confidence: 99%

Bile Salt Hydrolases: At the Crossroads of Microbiota and Human Health

et al. 2021

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The gut microbiota has been increasingly linked to metabolic health and disease over the last few decades. Several factors have been suggested to be involved in lipid metabolism and metabolic responses. One mediator that has gained great interest as a clinically important enzyme is bile salt hydrolase (BSH). BSH enzymes are widely distributed in human gastrointestinal microbial communities and are believed to play key roles in both microbial and host physiology. In this review, we discuss the current evidence related to the role of BSHs in health and provide useful insights that may pave the way for new therapeutic targets in human diseases.

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“…CDI is prevalent among elderly and immunocompromised individuals in healthcare settings, typically following treatment with broad spectrum antibiotics. However, the rate of community-acquired infections among healthy individuals has increased over the past two decades due to the emergence of novel epidemic C. difficile strains [3,4]. Despite the clinical importance of CDI, we do not have a complete understanding of molecular host-microbe interactions during infection, which hinders our progress towards developing effective prevention and treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection

et al. 2022

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Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. In addition to these symptoms, patients with CDI can develop severe inflammation and tissue damage, resulting in life-threatening toxic megacolon. CDI is mediated by two large homologous protein toxins, TcdA and TcdB, that bind and hijack receptors to enter host cells where they use glucosyltransferase (GT) enzymes to inactivate Rho family GTPases. GT-dependent intoxication elicits cytopathic changes, cytokine production, and apoptosis. At higher concentrations TcdB induces GT-independent necrosis in cells and tissue by stimulating production of reactive oxygen species via recruitment of the NADPH oxidase complex. Although GT-independent necrosis has been observed in vitro, the relevance of this mechanism during CDI has remained an outstanding question in the field. In this study we generated novel C. difficile toxin mutants in the hypervirulent BI/NAP1/PCR-ribotype 027 R20291 strain to test the hypothesis that GT-independent epithelial damage occurs during CDI. Using the mouse model of CDI, we observed that epithelial damage occurs through a GT-independent process that does not involve immune cell influx. The GT-activity of either toxin was sufficient to cause severe edema and inflammation, yet GT activity of both toxins was necessary to produce severe watery diarrhea. These results demonstrate that both TcdA and TcdB contribute to disease pathogenesis when present. Further, while inactivating GT activity of C. difficile toxins may suppress diarrhea and deleterious GT-dependent immune responses, the potential of severe GT-independent epithelial damage merits consideration when developing toxin-based therapeutics against CDI.

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From Nursery to Nursing Home: Emerging Concepts in Clostridioides difficile Pathogenesis

Cited by 13 publications

References 126 publications

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

Bile Salt Hydrolases: At the Crossroads of Microbiota and Human Health

Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection

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