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 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.
Published In/Presented At
Sangster, W., Hegarty, J. P., & Stewart, D. B., Sr (2015). Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics. Surgery, 157(1), 96–103. https://doi.org/10.1016/j.surg.2014.06.015
Medicine and Health Sciences
Department of Surgery