ArticleThe Journal of antimicrobial chemotherapy2013
The membrane as a target for controlling hypervirulent Clostridium difficile infections.
Article in The Journal of antimicrobial chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Repurposing azole antifungals as rapid bactericidal, membrane-disruptive therapeutics againstMicrobiology spectrum · 2026Article
- Development of a high-throughput screening platform forAntimicrobial agents and chemotherapy · 2026Article
- Evaluation of the antibacterial activity of the natural product α-mangostin against Clostridioides difficile.PloS one · 2026Article
- Clostridioides difficile Modifies its Aromatic Compound Metabolism in Response to Amidochelocardin-Induced Membrane Stress.mSphere · 2022Article
- Genetic Mechanisms of Vancomycin Resistance inAntibiotics (Basel, Switzerland) · 2022Review
- Ebselen Not Only Inhibits Clostridioides difficile Toxins but Displays Redox-Associated Cellular Killing.Microbiology spectrum · 2021Article
- (S)-Reutericyclin: Susceptibility Testing and In Vivo Effect on Murine Fecal Microbiome and Volatile Organic Compounds.International journal of molecular sciences · 2021Article
- Proteomic Adaptation ofCells · 2021Article
- A new phenothiazine derivate is active against Clostridioides difficile and shows low cytotoxicity.PloS one · 2021Article
- The Fatty Acid Synthesis Protein Enoyl-ACP Reductase II (FabK) is a Target for Narrow-Spectrum Antibacterials for Clostridium difficile Infection.ACS infectious diseases · 2019Article
- Synergy between Circular Bacteriocin AS-48 and Ethambutol against Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2018Article
- Article
- Chemical Genomics, Structure Elucidation, and in Vivo Studies of the Marine-Derived Anticlostridial Ecteinamycin.ACS chemical biology · 2017Article
- Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile.Scientific reports · 2016Article
- Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection.The Journal of antimicrobial chemotherapy · 2015Article
- Mode of action and bactericidal properties of surotomycin against growing and nongrowing Clostridium difficile.Antimicrobial agents and chemotherapy · 2015Article
- Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species.Antimicrobial agents and chemotherapy · 2015Article
- A curated C. difficile strain 630 metabolic network: prediction of essential targets and inhibitors.BMC systems biology · 2014Article
- Action of nitroheterocyclic drugs against Clostridium difficile.International journal of antimicrobial agents · 2014Article
- The Clostridium difficile proline racemase is not essential for early logarithmic growth and infection.Canadian journal of microbiology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesThe stationary phase of Clostridium difficile, which is primarily responsible for diarrhoeal symptoms, is refractory to antibiotic killing. We investigated whether disrupting the functions of the clostridial membrane is an approach to control C. difficile infections by promptly removing growing and non-growing cells.
methodsThe bactericidal activities of various membrane-active agents were determined against C. difficile logarithmic-phase and stationary-phase cultures and compared with known antibiotics. Their effects on the synthesis of ATP, toxins A/B and sporulation were also determined. The effect of rodent caecal contents on anti-difficile activities was examined using two reutericyclin lead compounds, clofazimine, daptomycin and other comparator antibiotics.
resultsMost membrane-active agents and partially daptomycin showed concentration-dependent killing of both logarithmic-phase and stationary-phase cultures. The exposure of cells to compounds at their MBC resulted in a rapid loss of viability with concomitant reductions in cellular ATP, toxins A/B and spore numbers. With the exception of nisin, these effects were not due to membrane pore formation. Interestingly, the activity of the proton ionophore nigericin significantly increased as the growth of C. difficile decreased, suggesting the importance of the proton gradient to the survival of non-growing cells. The activities of the lipophilic antimicrobials reutericyclins and clofazimine were reduced by caecal contents.
conclusionsThese findings indicate that C. difficile is uniquely susceptible to killing by molecules affecting its membrane function and bioenergetics, indicating that the clostridial membrane is a novel antimicrobial target for agents to alleviate the burden of C. difficile infections.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.