Article
Microbiology
Jacqueline R. Phan, Dung M. Do, Minh Chau Truong, Connie Ngo, Julian H. Phan, Shiv K. Sharma, Angel Schilke, Chrisabelle C. Mefferd, Jacob V. Villarama, Dengxun Lai, Amber Consul, Brian P. Hedlund, Steven M. Firestine, Ernesto Abel-Santos
Summary: Clostridioides difficile infection (CDI) is the major cause of antibiotic-associated diarrhea. Hypervirulent strains have led to increased CDI rates, and standard treatments are becoming less effective. The bile salt analog CaPA was found to be a better antigerminant than CamSA against different C. difficile strains, and it showed efficacy in preventing CDI in mice and hamsters.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Roua Almatrafi, Saeed Banawas, Mahfuzur R. Sarker
Summary: Spore germination is crucial in the development of Clostridium perfringens-associated food poisoning. A previous study found that dipicolinic acid (DPA) chelated with calcium (Ca-DPA) stimulates spore germination. This study aimed to explore the roles of Ca2+, Mn2+, and Mg2+ in spore germination. The results showed that Ca-DPA, but not DPA alone, induced C. perfringens spore germination. Additionally, spore-specific divalent cations Mn2+ and Mg2+, but not Zn2+, were found to induce spore germination.
Article
Food Science & Technology
Dong Liang, Shengnan Liu, Miaoyun Li, Yaodi Zhu, Lijun Zhao, Lingxia Sun, Yangyang Ma, Gaiming Zhao
Summary: In this study, nine commonly used food additives and four detergents were investigated for their effects on the growth of Clostridium perfringens spores. The results showed that ethylenediaminetetraacetate had a good inhibitory effect on spore growth, while tea polyphenols, D-isoascorbic acid, and potassium sorbate promoted leakage of contents during spore germination. Among the detergents, glutaraldehyde solution presented the best inhibitory effect on spore growth. Further analysis revealed that the bacteriostats could inactivate the spores by inhibiting germination or damaging the spore structure, preventing the formation of bacterial vegetative bodies.
Review
Infectious Diseases
Pei-Wen Wang, Wei-Ting Lee, Ya-Na Wu, Dar-Bin Shieh
Summary: Clostridioides difficile, a spore-forming bacterium, poses a serious health problem as a nosocomial infectious pathogen. Its spores have complex structures and dormant characteristics, contributing to their resistance to harsh environments. The vegetative cells produce endospores, and the mature spores are released from the hosts for dissemination of the pathogen.
Article
Microbiology
Marc Liggins, Norma Ramirez Ramirez, Ernesto Abel-Santos
Summary: Clostridium perfringens is an anaerobic, Gram-positive bacterium that forms spores to survive in harsh environments. It can germinate through two distinct pathways, the amino acid-only pathway and the bile salt/amino acid pathway. Different strains of C. perfringens have strain-specific spore formation requirements, but the germination responses are consistent among all strains.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Microbiology
Prabhat K. Talukdar, Mahfuzur R. Sarker
Summary: This study identified new sporulation and germination genes in Clostridium perfringens, and confirmed the importance of these genes in the processes of spore formation and germination.
Article
Immunology
Jen-Chieh Lee, Yuan -Pin Hung, Bo -Yang Tsai, Pei -Jane Tsai, Wen -Chien Ko
Summary: Severe CDIs in the ICU were not rare in this study. The ileus group tended to have more severe presentation, with severe and fulminant CDIs accounting for 65.2% and an ICU mortality rate of 39.1%. Clinicians should be aware of abdominal symptoms and signs other than diarrhea, such as ileus, for timely diagnosis and management of CDI.
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2021)
Article
Biotechnology & Applied Microbiology
Andrea Martinez Aguirre, Adegoke Oyeleye Adegbite, Joseph A. A. Sorg
Summary: The Clostridioides difficile pathogen can initiate infection through germination, which can be stimulated by certain amino acids and bile salts. We discovered that C. difficile strains have bile salt hydrolase activity, specifically towards taurine-derived bile salts. This activity can produce cholate, which signals the initiation of biofilm formation in C. difficile.
NPJ BIOFILMS AND MICROBIOMES
(2022)
Article
Microbiology
Siqi Wang, Leyang Xiang, Fang li, Wenlin Deng, Pinjing Lv, Ye Chen
Summary: This study found that levels of fecal short-chain fatty acids (SCFAs), particularly butyrate, are reduced, and normal colon structure is damaged in patients with CDI compared with those in healthy individuals. Bile acid (BA) metabolic disorder in patients with CDI is characterized by increased primary BA levels and decreased secondary BAs. Butyrate treatment may serve as a novel therapeutic approach for patients with CDI.
MICROBIOLOGY SPECTRUM
(2023)
Article
Gastroenterology & Hepatology
Anqi Jin, Tony Chien, Qiwen Huang, Pragati Kenkare, Mai Vu, Sandra Wilson, Edward S. Huang
Summary: The study found that cholecystectomy is associated with a slightly increased risk of incident CDI, but this effect is not influenced by the use of proton pump inhibitors, antibiotics, or hospitalization.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Christopher Yip, Naomi C. Okada, Amber Howerton, Amei Amei, Ernesto Abel-Santos
Summary: The synthetic bile salt CamSA shows potential in preventing Clostridioides difficile infections, offering multi-day protection with a single dose in mice. Its pharmacokinetic properties suggest limited systemic absorption and a slow-release mechanism through cycling between the liver and intestines. This unique pattern of protection may be attributed to CamSA's stability in the gut of antibiotic-treated mice and degradation by the microbiota in non-antibiotic treated animals.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Food Science & Technology
Siobhan McSharry, Leonard Koolman, Paul Whyte, Declan Bolton
Summary: This study identified that disinfectants 2, 7, and 10 were the most effective in eliminating Clostridium spores in the meat plant environment, with D-values ranging from 2.1 to 8.4 min at 20 degrees C.
Review
Microbiology
Abbas Yadegar, Sepideh Pakpoor, Fathima F. Ibrahim, Ali Nabavi-Rad, Laura Cook, Jens Walter, Anna M. Seekatz, Karen Wong, Tanya M. Monaghan, Dina Kao
Summary: Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI), but the mechanisms behind its efficacy are not fully understood. This paper provides an overview of rCDI pathogenesis and discusses potential mechanisms of action, including microbial, metabolic, immunological, and epigenetic mechanisms. The authors also outline research gaps and recommend methodological improvements for future studies to better understand and develop targeted therapies to replace FMT.
CELL HOST & MICROBE
(2023)
Article
Microbiology
Hailee N. Nerber, Joseph A. Sorg
Summary: Clostridioides difficile spores are resilient and can survive extreme conditions, making their elimination from the environment difficult. Small acid-soluble proteins (SASPs) play a role in spore resistance in model spore-forming organism Bacillus subtilis, with SspA and SspB found to be essential for UV resistance and spore formation regulation in C. difficile.
Article
Biochemistry & Molecular Biology
Tadakuni Monma, Junichi Iwamoto, Akira Honda, Hajime Ueda, Fumio Kakizaki, Shoichiro Yara, Teruo Miyazaki, Tadashi Ikegami
Summary: The ratio of secondary bile acids in serum can serve as a biomarker for predicting susceptibility to Clostridium difficile infection, with levels below a certain threshold indicating a higher risk of CDI.
Article
Biotechnology & Applied Microbiology
Alexandra M. Mowday, Ludwig J. Dubois, Aleksandra M. Kubiak, Jasmine V. E. Chan-Hyams, Christopher P. Guise, Amir Ashoorzadeh, Philippe Lambin, David F. Ackerley, Jeff B. Smaill, Nigel P. Minton, Jan Theys, Adam V. Patterson
Summary: The study investigated the ability of Neisseria meningitidis type I nitroreductase (NmeNTR) to metabolize the prodrug PR-104A in an in vivo model of Clostridium Directed Enzyme Prodrug Therapy (CDEPT). It showed that human colon cancer cells overexpressing NmeNTR exhibited sensitivity to PR-104A and imaging agent EF5, and colonization of NmeNTR-expressing Clostridium sporogenes in necrotic tissues demonstrated moderate anti-tumor activity when treated with prodrugs. Successful preclinical evaluation of a transferable gene for dual metabolism of imaging agents and prodrugs is a crucial step towards clinical evaluation of CDEPT.
CANCER GENE THERAPY
(2022)
Article
Microbiology
Jorge Monteford, Terry W. Bilverstone, Patrick Ingle, Sheryl Philip, Sarah A. Kuehne, Nigel P. Minton
Summary: Clostridioides difficile R20291 is the most studied PCR-Ribotype 027 isolate, and its two predominant lineages show substantive phenotypic differences and slight differences in genomes. Considering the source of R20291 is important for research outcomes.
Article
Biotechnology & Applied Microbiology
Alexander Mook, Matthias H. Beck, Jonathan P. Baker, Nigel P. Minton, Peter Durre, Frank R. Bengelsdorf
Summary: This study aimed to construct and characterize Acetobacterium woodii strains capable of autotrophic lactate production by knocking out genes responsible for lactate consumption and expressing a d-lactate dehydrogenase gene from Leuconostoc mesenteroides. Additionally, the study introduced a fluorescence-based reporter tool to quickly analyze gene expression and optimize production strains.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Callum McGregor, Nigel P. Minton, Katalin Kovacs
Summary: Polyhydroxyalkanoates are promising alternatives to traditional plastics, and their properties can be enhanced by coproducing with 3-hydroxypropionate to form a copolymer. Utilizing pathway design and gene overexpression can optimize the incorporation of 3-hydroxypropionate into the copolymer. Deletion of specific genes can also increase the proportion of 3-hydroxypropionate in the copolymer.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Craig Woods, Christopher M. Humphreys, Claudio Tomi-Andrino, Anne M. Henstra, Michael Kopke, Sean D. Simpson, Klaus Winzer, Nigel P. Minton
Summary: Most bacterial genes remain poorly characterized, and transposon insertion sequencing is a high-throughput technique that can help rectify this deficiency, although it is limited to species with efficient DNA transfer procedures. Researchers have developed approaches to overcome this barrier in autotrophic species, enabling the determination of essential genes required for utilizing carbon monoxide as the sole carbon and energy source.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Correction
Multidisciplinary Sciences
Pablo Castro-Cordova, Paola Mora-Uribe, Rodrigo Reyes-Ramirez, Glenda Cofre-Araneda, Josue Orozco-Aguilar, Christian Brito-Silva, Maria Jose Mendoza-Leon, Sarah A. Kuehne, Nigel P. Minton, Marjorie Pizarro-Guajardo, Daniel Paredes-Sabja
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Barbara Bourgade, Christopher M. Humphreys, James Millard, Nigel P. Minton, M. Ahsanul Islam
Summary: This study presents a novel synthetic biochemical pathway to convert acetate into ethylene glycol (EG) in gas-fermenting acetogen Clostridium autoethanogenum. The research team developed a computational workflow to design and analyze numerous novel pathways for EG production, and successfully constructed the pathway in the chosen host organism. This work serves as an important proof-of-concept approach to computationally design and experimentally implement fully synthetic metabolic pathways.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemical Research Methods
Ivana Cengic, Ines C. Canadas, Nigel P. Minton, Elton P. Hudson
Summary: In this study, a theophylline-responsive riboswitch-induced CRISPR/Cas9 system was developed for precise and markerless genome editing in cyanobacterium. This single-vector system enables multiplexed editing and allows for the generation of markerless mutants.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Microbiology
Guillaume Pregnon, Nigel P. Minton, Philippe Soucaille
Summary: E. limosum B2, an acetogen capable of producing butyrate and acetate from methanol, was subjected to adaptive laboratory evolution on methanol mineral medium. The evolved populations showed a significant increase in growth rate and exhibited changes in protein and methylome profiles, indicating the involvement of epigenetic regulation in metabolic improvements.
Article
Biochemical Research Methods
Bashir L. Rumah, Benedict H. Claxton Stevens, Jake E. Yeboah, Christopher E. Stead, Emily L. Harding, Nigel P. Minton, Ying Zhang
Summary: In this study, a CRISPR/Cas9 genome editing system was constructed and successfully utilized to delete and insert genes in two types of methanotrophic bacteria, Methylococcus capsulatus Bath and Methylocystis parvus OBBP. The combination of homology-directed repair achieved high frequencies of gene deletions and insertions. Various parameters were also investigated to optimize the CRISPR/Cas9 system in Methylocystis parvus OBBP. This work demonstrated the first efficient CRISPR/Cas9 system generating scarless clean gene deletions and insertions in methanotroph genomes.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Immunology
Alexander M. Rawson, Andrew W. Dempster, Christopher M. Humphreys, Nigel P. Minton
Summary: Clostridium botulinum is a bacteria that is classified based on its ability to produce botulinum neurotoxin (BoNT). BoNT is the main virulence factor and the cause of botulism, a potentially fatal disease characterized by paralysis. The BoNT is used for medical treatments and in the cosmetic industry due to its potency and specificity.
Article
Microbiology
James Millard, Alexander Agius, Ying Zhang, Philippe Soucaille, Nigel Peter Minton
Summary: Targeted mutations in Eubacterium limosum were achieved using an inducible counter-selective system combined with a non-replicative integrating mutagenesis vector. This system allowed for precise gene deletions, including genes involved in histidine biosynthesis, methanol metabolism, and L-carnitine demethylation. The desired mutants could be obtained with only one induction step after the initial selection of transformant colonies. This approach enables quick and efficient gene editing of E. limosum.
Article
Biotechnology & Applied Microbiology
Barbara Bourgade, James Millard, Christopher M. Humphreys, Nigel P. Minton, M. Ahsanul Islam
Summary: This study demonstrates the significance of a replicating shuttle vector for genetic and metabolic engineering in industrially important M. thermoacetica. The vector was successfully applied for non-native ethanologenesis, allowing ethanol production in this organism.
FERMENTATION-BASEL
(2022)
Article
Microbiology
M. J. Whittle, T. W. Bilverstone, R. J. van Esveld, A. C. Luecke, M. M. Lister, S. A. Kuehne, N. P. Minton
Summary: Bacteriophages show promise as an alternative treatment for Clostridioides difficile infection. Researchers isolated four novel C. difficile myoviruses, including Phi CD1801, which demonstrated broad host range activity against relevant strains. The study also identified SIpA as a potential phage receptor, highlighting the need for further research on phages with activity against specific bacterial strains. These findings provide important insights for the development of effective phage therapy for C. difficile infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biotechnology & Applied Microbiology
Kamran Jawed, Victor Uhunoma Irorere, Rajesh Reddy Bommareddy, Nigel P. Minton, Katalin Kovacs
Summary: The facultative chemolithoautotroph Cupriavidus necator H16 can grow aerobically with organic substrates or H-2 and CO2, and accumulate a large amount of poly (3-hydroxybutyrate) (PHA). This study investigated the ability of this organism to co-utilize volatile fatty acids (VFAs) and CO2 for carbon sources under mixotrophic growth conditions, and monitored PHA production. The results showed that PHA accumulation was significantly higher when cultures were grown mixotrophically with H-2 as an additional energy source. A two-step VFA feeding regime using a VFA mixture derived from an anaerobic digestor (AD) was found to be the most effective method for PHA accumulation.
FERMENTATION-BASEL
(2022)