title: Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics.
abstract: 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.
  
  
  CONCLUSIONS
  PTLPs demonstrate capability in eradicating C difficile in vitro, and with further development, may represent an organism-specific, microbiome-sparing therapy for CDI.
authors: Division of Colorectal Surgery, Penn State Hershey Medical Center, Hershey, PA.
authors: William
authors: W
authors: Sangster
authors: Division of Colorectal Surgery, Penn State Hershey Medical Center, Hershey, PA.
authors: John P
authors: JP
authors: Hegarty
authors: Division of Colorectal Surgery, Penn State Hershey Medical Center, Hershey, PA. Electronic address: dstewart@hmc.psu.edu.
authors: David B
authors: DB
authors: Stewart
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000235:genetics / Q000378:metabolism*; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D021521:Ribotyping; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins