SILVER SPRING, Md. (NNS) -- Naval Medical Research Center (NMRC) scientists presented their bacteriophage (phage) bioinformatics pipeline during the 2019 Evergreen Phage Meeting at Evergreen State College in Olympia, Washington August 4.
According to Dr. Kimberly Bishop-Lilly, head of Genomics & Bioinformatics department, phages are viruses that infect bacteria. The ability to effectively target and kill bacteria has led to the use of phages to treat bacterial infections (referred to as phage therapy). When a lytic phage infects a bacterium, it reproduces inside and kills it. Interest in phage therapy has peaked due to the increasing prevalence of antibiotic resistant bacteria or multidrug resistant (MDR) infections and the decreasing rate of discovery of new antibiotics. In order to treat a diverse array of bacterial infections, a large and diverse collection of phages needed to be amassed.
“Research aimed at making phage therapy for MDR infections a reality is very relevant to Navy operations,” said Bishop-Lilly. “Just like what is occurring in the civilian population in communities and hospitals around the world, our warfighters have experienced steady increases in MDR infections, including bacterial infections in casualties from Iraq and Afghanistan.”
For the past two years, NMRC’s Genomics and Bioinformatics Department has developed an archive to genetically characterize phages from sequencing data and determine if they are suitable for therapeutic use. They use a robust bioinformatics workflow, and standards they created for quality and safety. To date, almost 250 diverse phages for a number of pathogens, including many such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have been categorized.
According to Dr. Biswajit Biswas, chief of the phage division, while this pipeline automates much of the process, manual analysis is still required at various checkpoints.
“Checkpoints in the workflow are concerned with detection of various classes of deleterious genes, such as those encoding for antibiotic resistance, toxins, bacterial virulence factors, or proteins involved with prophage integration/lifestyle,” said Biswas.
The pipeline the researchers use combines dozens of tools and databases to discover problematic areas of the phage genomes; areas which represent potential risk to a patient, such as toxins or antibiotic resistance genes, with high sensitivity.
“This pipeline has allowed us to perform this characterization quickly and efficiently without sacrificing the sensitivity of the genetic safety assessment,” Bishop-Lilly said.
During the presentation, the scientists explained how each unique phage added to their collection increases the chance the library can be used to develop a personalized treatment for a specific warfighter battling a bacterial infection.
“We have a long way to go to make phage gene annotations more informative for therapeutic applications and consistent among different projects,” said Biswas. “More efforts to improve phage gene annotation in the future are necessary and should ideally be accompanied by transcriptome sequencing experiments and protein characterization.”
Currently, the phages and genetic data are being shared with a commercial partner to assess the practical applicability in human clinical trials.
About Naval Medical Research Center
NMRC's eight laboratories are engaged in a broad spectrum of activity from basic science in the laboratory to field studies at sites in austere and remote areas of the world to operational environments. In support of the Navy, Marine Corps and joint U.S. warfighters, researchers study infectious diseases, biological warfare detection and defense, combat casualty care, environmental health concerns, aerospace and undersea medicine, medical modeling, simulation and operational mission support, and epidemiology and behavioral sciences.
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