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Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions
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Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions

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

Deadline for manuscript submissions: closed (20 January 2025) | Viewed by 17150

Special Issue Editors

Dr. Xiaolun Sun

E-Mail Website
Guest Editor
The Center of Excellence for Poultry Science & Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR, USA
Interests: host-microbe interactions at the gastrointestinal tract (inflammatory bowel diseases; necrotic enteritis; Campylobacteriosis; colorectal cancer)
Special Issues, Collections and Topics in MDPI journals
Dr. Zhenquan Jia

E-Mail Website
Guest Editor
Department of Biology, The University of North Carolina at Greensboro, Greensboro, NC, USA
Interests: environmental-factor-induced vascular inflammation and injury (understanding the signaling mechanisms)
Special Issues, Collections and Topics in MDPI journals
Dr. Ying Fu

E-Mail Website
Guest Editor
Cell and Molecular Biology Program & The Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, USA
Interests: host-microbe interactions at the gastrointestinal tract (necrotic enteritis; Campylobacteriosis; vaccination)

Special Issue Information

Dear Colleagues,

The genus Clostridium is a group of Gram-positive, spore-forming, and anaerobic bacteria. Clostridium inhabits a large spectrum of environments, such as soil, water, and the intestinal tracts of humans as well as animals. A diverse array of diseases, such as enteritis, gas gangrene, and tetanus, are induced by the members of exotoxin-producing Clostridium, such as C. difficile, C. perfringens, C. botulinum, C. tetani, C. chauvoei, C. haemolyticum, C. novyi, and C. septicum. Although an increasingly large body of studies has brought significant insights into the mechanisms of Clostridium diseases, much knowledge remains to be elucidated regarding the dynamic interactions between Clostridium, environments (microbiomes), and hosts at the levels of genomics, transcriptomics, proteomics, and metabolomics. 

The goal of this Special Issue, entitled “Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions”, is to promote reports of advanced findings in the mechanisms and interventions of Clostridium diseases. 

Both original research and review articles regarding Clostridium pathogenesis are welcomed. Potential topics include, but are not limited to, the following:

  • Clostridium virulence factors;
  • Microbiota and metabolome in Clostridium diseases;
  • Host responses to Clostridium diseases;
  • Environmental factors of Clostridium diseases;
  • Interventions to reduce Clostridium pathogenesis.

Dr. Xiaolun Sun
Dr. Zhenquan Jia
Dr. Ying Fu
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 2200 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

  • Clostridium virulence
  • microbiome
  • host response
  • intervention
  • pathogenesis

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Published Papers (6 papers)

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Research

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14 pages, 1090 KiB  
Article
Identification of Germinants and Expression of Germination Genes in Clostridium perfringens Strains Isolated from Diarrheic Animals
by Prabhat K. Talukdar, Maryam Alnoman and Mahfuzur R. Sarker
Pathogens 2024, 13(3), 194; https://doi.org/10.3390/pathogens13030194 - 22 Feb 2024
Cited by 1 | Viewed by 1762
Abstract
In this study, we investigated the spore germination phenotype of Clostridium perfringens strains isolated from diarrheic animals (animal strains). The transcripts of germination-specific genes and their protein products were also measured. Our study found the following results: (i) animal strains spores germinated at [...] Read more.
In this study, we investigated the spore germination phenotype of Clostridium perfringens strains isolated from diarrheic animals (animal strains). The transcripts of germination-specific genes and their protein products were also measured. Our study found the following results: (i) animal strains spores germinated at a slower rate with AK (mixture of L-asparagine and KCl), L-cysteine, or L-lysine, but the extent of germination varied based on strains and germinants used; (ii) none of the amino acids (excluding L-cysteine and L-lysine) were identified as a universal germinant for spores of animal strains; (iii) animal strain spores germinated better at a pH range of 6.0–7.0; (iv) all tested germination-specific genes were expressed in animal strains; the levels of expression of major germinant receptor gene (gerKC) were higher and the cortex hydrolysis machinery genes (cspB and sleC) were lower in animal strains, compared to the food poisoning strain SM101; and (v) the levels of CspB and SleC were significantly lower in spores of animal strains compared to strain SM101, suggesting that these animal strains lack an efficient spore cortex hydrolysis machinery. In summary, our findings suggest that the poor or slow spore germination in C. perfringens animal strains might be due to incomplete spore cortex hydrolysis. Full article
(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)
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15 pages, 2192 KiB  
Article
Potent Bile Acid Microbial Metabolites Modulate Clostridium perfringens Virulence
by Tahrir Alenezi, Ying Fu, Bilal Alrubaye, Thamer Alanazi, Ayidh Almansour, Hong Wang and Xiaolun Sun
Pathogens 2023, 12(10), 1202; https://doi.org/10.3390/pathogens12101202 - 28 Sep 2023
Cited by 3 | Viewed by 2172
Abstract
Clostridium perfringens is a versatile pathogen, inducing diseases in the skin, intestine (such as chicken necrotic enteritis (NE)), and other organs. The classical sign of NE is the foul smell gas in the ballooned small intestine. We hypothesized that deoxycholic acid (DCA) reduced [...] Read more.
Clostridium perfringens is a versatile pathogen, inducing diseases in the skin, intestine (such as chicken necrotic enteritis (NE)), and other organs. The classical sign of NE is the foul smell gas in the ballooned small intestine. We hypothesized that deoxycholic acid (DCA) reduced NE by inhibiting C. perfringens virulence signaling pathways. To evaluate the hypothesis, C. perfringens strains CP1 and wild-type (WT) HN13 and its mutants were cultured with different bile acids, including DCA and isoallolithocholic acid (isoalloLCA). Growth, hydrogen sulfide (H2S) production, and virulence gene expression were measured. Notably, isoalloLCA was more potent in reducing growth, H2S production, and virulence gene expression in CP1 and WT HN13 compared to DCA, while other bile acids were less potent compared to DCA. Interestingly, there was a slightly different impact between DCA and isoalloLCA on the growth, H2S production, and virulence gene expression in the three HN13 mutants, suggesting possibly different signaling pathways modulated by the two bile acids. In conclusion, DCA and isoalloLCA reduced C. perfringens virulence by transcriptionally modulating the pathogen signaling pathways. The findings could be used to design new strategies to prevent and treat C. perfringens-induced diseases. Full article
(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)
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16 pages, 2126 KiB  
Article
Pathogenicity and Antibiotic Resistance Diversity in Clostridium perfringens Isolates from Poultry Affected by Necrotic Enteritis in Canada
by Sara García-Vela, Agustí Martínez-Sancho, Laila Ben Said, Carmen Torres and Ismail Fliss
Pathogens 2023, 12(7), 905; https://doi.org/10.3390/pathogens12070905 - 3 Jul 2023
Cited by 10 | Viewed by 3801
Abstract
Necrotic enteritis (NE) caused by C. perfringens is one of the most common diseases of poultry and results in a huge economic loss to the poultry industry, with resistant clostridial strains being a serious concern and making the treatment difficult. Whole-genome sequencing approaches [...] Read more.
Necrotic enteritis (NE) caused by C. perfringens is one of the most common diseases of poultry and results in a huge economic loss to the poultry industry, with resistant clostridial strains being a serious concern and making the treatment difficult. Whole-genome sequencing approaches represent a good tool to determine resistance profiles and also shed light for a better understanding of the pathogen. The aim of this study was to characterize, at the genomic level, a collection of 20 C. perfringens isolates from poultry affected by NE, giving special emphasis to resistance mechanisms and production of bacteriocins. Antimicrobial resistance genes were found, with the tet genes (associated with tetracycline resistance) being the most prevalent. Interestingly, two isolates carried the erm(T) gene associated with erythromycin resistance, which has only been reported in other Gram-positive bacteria. Twelve of the isolates were toxinotyped as type A and seven as type G. Other virulence factors encoding hyaluronases and sialidases were frequently detected, as well as different plasmids. Sequence types (ST) revealed a high variability of the isolates, finding new allelic combinations. Among the isolates, C. perfringens MLG7307 showed unique characteristics; it presented a toxin combination that made it impossible to toxinotype, and, despite being identified as C. perfringens, it lacked the housekeeping gene colA. Genes encoding bacteriocin BCN5 were found in five isolates even though no antimicrobial activity could be detected in those isolates. The bcn5 gene of three of our isolates was similar to one previously reported, showing two polymorphisms. Concluding, this study provides insights into the genomic characteristics of C. perfringens and a better understanding of this avian pathogen. Full article
(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)
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Review

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16 pages, 1394 KiB  
Review
Recognition, Diagnosis, and Treatment of Clostridioides difficile Enterocolitis Presenting Without Diarrhea: A Literature Review
by Ezgi Yılmaz, Duygu Işıl Gencer, Mustafa Salih Akın, Meyha Şahin, Bahadır Ceylan and Ali Mert
Pathogens 2025, 14(2), 181; https://doi.org/10.3390/pathogens14020181 - 12 Feb 2025
Viewed by 740
Abstract
Diarrhea, as the well-known clinical feature of Clostridioides difficile infection (CDI), may be absent at the initial presentation, leading to delays in diagnosis. The delay is due to both underrecognition of such presentations and the dependence of CDI diagnosis on stool samples. This [...] Read more.
Diarrhea, as the well-known clinical feature of Clostridioides difficile infection (CDI), may be absent at the initial presentation, leading to delays in diagnosis. The delay is due to both underrecognition of such presentations and the dependence of CDI diagnosis on stool samples. This review was conducted to evaluate the literature for CDI cases presenting without diarrhea, raise awareness about the possibility of CDI in the differential diagnosis regardless of diarrhea, and assemble relevant data to harmonize clinical approaches. The PubMED Medline database was used to conduct this literature review, focusing on reported CDI cases presenting without diarrhea. After exclusions, 22 articles were included for analysis, providing data for 48 cases. This paper will present the selected clinical data of these 48 patients and follow a real-life case with a clinical course of CDI including presentation, diagnosis, management, and outcomes. The excessive mortality and bowel resection rates of CDI patients presenting without diarrhea were the notable findings. Poor prognosis was possibly inflated by delayed diagnoses in an unfamiliar setting, emphasizing the importance of a high index of suspicion to allow early recognition of CDIs in the appropriate clinical context despite the absence of diarrhea. Full article
(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)
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26 pages, 1432 KiB  
Review
Clostridioides difficile and Gut Microbiota: From Colonization to Infection and Treatment
by Patrizia Spigaglia
Pathogens 2024, 13(8), 646; https://doi.org/10.3390/pathogens13080646 - 31 Jul 2024
Cited by 9 | Viewed by 5199
Abstract
Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from [...] Read more.
Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile’s role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota. Full article
(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)
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15 pages, 326 KiB  
Review
Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia—A Literature Review
by Adrian Boicean, Dan Bratu, Ciprian Bacila, Ciprian Tanasescu, Radu Sorin Fleacă, Calin Ilie Mohor, Andra Comaniciu, Teodora Băluță, Mihai Dan Roman, Radu Chicea, Adrian Nicolae Cristian, Adrian Hasegan, Sabrina Birsan, Horațiu Dura and Cosmin Ioan Mohor
Pathogens 2023, 12(6), 766; https://doi.org/10.3390/pathogens12060766 - 26 May 2023
Cited by 14 | Viewed by 2350
Abstract
In a mutually beneficial connection with its host, the gut microbiota affects the host’s nutrition, immunity, and metabolism. An increasing number of studies have shown links between certain types of disease and gut dysbiosis or specific microorganisms. Fecal microbiota transplantation (FMT) is strongly [...] Read more.
In a mutually beneficial connection with its host, the gut microbiota affects the host’s nutrition, immunity, and metabolism. An increasing number of studies have shown links between certain types of disease and gut dysbiosis or specific microorganisms. Fecal microbiota transplantation (FMT) is strongly advised for the treatment of recurrent or resistant Clostridium difficile infection (CDI) due to its outstanding clinical effectiveness against CDI. The therapeutic potential of FMT for other disorders, particularly inflammatory bowel diseases and malignancies, is currently gaining more and more attention. We summarized the most recent preclinical and clinical evidence to show the promise of FMT in the management of cancer as well as complications related to cancer treatment after reviewing the most recent research on the gut microbiota and its relationship to cancer. Full article
(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)
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