Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics

Background Current Clostridium difficile infection (CDI) antibiotic regimens have become increasingly ineffective at achieving cure and preventing recurrence. A recently developed alternative to conventional antibiotics are phage tail-like particles (PTLPs), which are proteins that are morphological...

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Bibliographic Details
Published in:Surgery 2015-01, Vol.157 (1), p.96-103
Main Authors: Sangster, William, MD, Hegarty, John P., PhD, Stewart, David B., MD, FACS, FASCRS
Format: Article
Language:English
Subjects:
Bacterial Proteins - metabolism
Bacterial Proteins - therapeutic use
Clostridium difficile - genetics
Clostridium difficile - metabolism
Enterocolitis, Pseudomembranous - drug therapy
Humans
Microbial Sensitivity Tests
Ribotyping
Sequence Analysis, DNA
Surgery
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Summary:Background Current Clostridium difficile infection (CDI) antibiotic regimens have become increasingly ineffective at achieving cure and preventing recurrence. A recently developed alternative to conventional antibiotics are phage tail-like particles (PTLPs), which are proteins that are morphologically similar to bacteriophages and are produced by C difficile . This study examines the in vitro killing spectrum of a previously unreported PTLP isolated from a clinical isolate of C difficile. Methods Using patient-derived samples from an institutional review board-approved C difficile tissue bank, a ribotype 078  C difficile isolate was anaerobically incubated on blood agar plates that were preswabbed with norfloxacin to induce the production of PTLPs. Concentrated PTLP populations were confirmed using transmission electron microscopy. Using a standard lawn spot approach, bactericidal activity was assessed as indicated by a clearing within the bacterial lawn. The PTLP genomic cluster was also fully sequenced and open reading frames were annotated according to predicted function. Results PTLPs were assessed using 64 patient-derived C difficile isolates of varying ribotypes. PTLPs demonstrated complete bactericidal activity in 21 of 25 ribotype 027 isolates with partial activity in 2 of the 25. Complete bactericidal activity was not demonstrated against any other ribotype or non- difficile bacteria, suggesting a species and ribotype specificity. Functional genes, which may be necessary for killing, were identified within the PTLP genetic locus. Conclusion PTLPs demonstrate capability in eradicating C difficile in vitro, and with further development, may represent an organism-specific, microbiome-sparing therapy for CDI.
ISSN:0039-6060
1532-7361
DOI:10.1016/j.surg.2014.06.015