New Insights into Clostridioides difficile Pathogenesis and Novel Treatment Strategies

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 7332

Special Issue Editors


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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

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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

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Keywords

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

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Published Papers (2 papers)

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Research

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8 pages, 1966 KiB  
Communication
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 3 | Viewed by 2305
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 [...] Read more.
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
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Review

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14 pages, 693 KiB  
Review
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 11 | Viewed by 4207
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 [...] Read more.
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
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