The Centers for Disease Control and Prevention have estimated that each year, two million people in the United States become infected with antibiotic-resistant bacteria, of which, approximately 23000 die as a direct result of these infections. Phage therapy, or the treatment of bacterial infection by specific, antagonistic viruses, provides one alternative to traditional antibiotics. Bacteriophages, or phages, are bacteria-specific viruses that possess biological traits that allow for not only the removal of bacterial infection, but also the evasion of bacterial resistance, which renders antibiotics ineffective. Previous research has shown the addition of iron-doped apatite nanoparticles (IDANPs) to bacteria prior to phage exposure results in increased bacterial plaques in vitro. Coupled with the biocompatible nature of apatite, these results provide promise for future use of IDANPs as adjuvants to phage therapy along with anti-bacterial applications yet to be explored. Although IDANP enhancement of phage infection has been replicated many times in gram-positive and gram-negative prokaryotic hosts as well as with the utilization of both RNA and DNA viruses, the specific mechanisms involved remain elusive. To further understand increased phage infections in a prokaryotic system, and to evaluate the safety of IDANPs as a treatment used in a eukaryotic system, we have replicated plaque assay experiments in an algal system using Chlorella variabilis NC64A and its virus, Paramecium bursaria chlorella virus 1 (PBCV-1). Statistical modeling was used to evaluate alteration in numbers of plaques observed after viral introduction in IDANP-exposed versus non-IDANP-exposed bacterial and algal cell cultures. While IDANPs synthesized between 25°C-45°C and doped with 30% iron have been shown to influence dramatic increases in phage-induced bacterial death, experiments replicated in an algal system indicated viral infections do not increase when C. variabilis cells are pre-exposed to IDANPs. It is essential to potential use of IDANPs as an antibacterial adjuvant that IDANPs do not increase viral infection of eukaryotic host cells during treatment.
Interest in phage therapy is currently on the rise. As bacterial strains become more and more resistant to antibiotic treatment, research into improved and alternative methods for treating bacterial disease becomes increasingly pertinent. Bacteriophages, or simply phage, are bacteria-specific viruses that provide an alternative treatment in addition to possessing biological traits that allow them avoid bacterial resistance. The authors have found specific apatite nanoparticles exhibit an unprecedented effect on phage infections in vitro. Through the addition of 30% iron-doped apatite nanoparticles (IDANPs) to phage in solution, bacterial death zone (plaque) totals increase up to 128% higher than phage alone. These results are therefore of great interest for antibacterial applications. Extensive investigations and characterization evaluations of these IDANPs and mechanisms involved are an ongoing focus and effort of our researchers. In this article, the authors describe and document the in vitro and characterization results they have amassed thus far.
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