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New Insights into Clostridioides difficile Pathogenesis and Novel Treatment Strategies

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Special Issue Editors

Dr. I-Hsiu Huang

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Guest Editor

Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107, USA
Interests: Clostridioides difficile; host–pathogen interaction; vaccine development; antimicrobial discovery

Dr. Jenn Wei Chen

E-Mail Website
Guest Editor

Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan
Interests: Bacterial pathogenesis, microbiota research

Special Issue Information

Dear Colleagues,

The anaerobic spore forming pathogen Clostridioides difficile is the leading cause of antibiotic-associated diarrhea (AAD) worldwide. Since its discovery in 1975 as the causative agent of AAD and pseudomembranous colitis, C. difficile outbreaks have been reported worldwide. C. difficile can persist as hardy stress-resistant spores that germinate in the host intestine upon encounter with bile acids and other co-germinants. Once germinated, C. difficile produces three protein toxins, TcdA and TcdB, and a transferase toxin CDT. TcdA and TcdB are the major virulence factors that act on host cells via the inactivation of Rho proteins, which results in eventual loss of epithelial tight junctions, cellular apoptosis, and inflammation. Although extensive studies have revealed the role of C. difficile toxins in pathogenesis, less is known about the functions of other C. difficile virulence factors such as spores, flagella, and other cell wall proteins that might participate in pathogen–host interaction. In the midst of the COVID-19 pandemic, in which the elderly population is most at risk, similar symptoms associated with both CDI and COVID-19 can delay proper diagnosis and treatment of either infection. The high relapse rate associated with C. difficile infections (CDI) and the multi-antibiotic resistant nature of the pathogen also strongly indicate that alternative treatment strategies need to be developed and made available soon.

In this Special Issue, we will accept a wide range of manuscripts (including original research articles and reviews) that address new pathogenic mechanisms, transmission routes, and novel preventive or treatment strategies.

We look forward to your contribution.

Dr. I-Hsiu Huang
Dr. Jenn Wei Chen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Clostridioides difficile
Host–pathogen interaction
Microbiome
Antimicrobial
Vaccine
Disease transmission
Environmental reservoir

Published Papers (2 papers)

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Research

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8 pages, 1966 KiB

Open AccessCommunication

IL-16 and BCA-1 Serum Levels Are Associated with Disease Severity of C. difficile Infection

by Dor Gotshal, Maya Azrad, Zohar Hamo, Orna Nitzan and Avi Peretz

Pathogens 2021, 10(5), 631; https://doi.org/10.3390/pathogens10050631 - 20 May 2021

Cited by 2 | Viewed by 1973

Abstract

Clostridioides difficile infection (CDI) is associated with a high risk for complications and death, which requires identifying severe patients and treating them accordingly. We examined the serum level of six cytokines and chemokines (IL-16, IL-21, IL-23, IL-33, BCA-1, TRAIL) and investigated the association between them and patients’ disease severity. Concentrations of six cytokines and chemokines were measured using the MILLIPLEX^®MAP kit (Billerica, MA, USA) in serum samples attained from CDI patients within 24–48 h after laboratory confirmation of C. difficile presence. Demographic and clinical data were collected from medical records. The disease severity score was determined according to guidelines of the “Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America” (SHEA-IDSA). Out of 54 patients, 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. IL-16 (p = 0.005) and BCA-1 (p = 0.012) were associated with a more severe disease. In conclusion, IL-16 and BCA-1, along with other cytokines and chemokines, may serve as biomarkers for the early prediction of CDI severity in the future. An improved and more accessible assessment of CDI severity will contribute to the adjustment of the medical treatment, which will lead to a better patient outcome. Full article

(This article belongs to the Special Issue New Insights into Clostridioides difficile Pathogenesis and Novel Treatment Strategies)

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Review

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14 pages, 693 KiB

Open AccessReview

Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents

by Chun-Wei Chiu, Pei-Jane Tsai, Ching-Chi Lee, Wen-Chien Ko and Yuan-Pin Hung

Pathogens 2021, 10(6), 649; https://doi.org/10.3390/pathogens10060649 - 24 May 2021

Cited by 10 | Viewed by 3787

Abstract

Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future. Full article

(This article belongs to the Special Issue New Insights into Clostridioides difficile Pathogenesis and Novel Treatment Strategies)

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