Bacteriophage Therapies to Prevent and Treat Diarrhea in Military Personnel
Abstract
The proposed research project addresses Fiscal Year 2016 Peer Reviewed Medical Research Program Topic of Antimicrobial Resistance, specifically, research on the use of bacteriophages to treat antibiotic-resistant bacteria. Individuals in the military travel to exotic countries when deployed and, once there, are at an increased risk of contracting diarrhea-causing infections (i.e., travelers diarrhea) from local food and/or unsanitary conditions. Diarrhea is often caused by bacteria that infect the lining of the intestines, and although most healthy individuals can survive these infections without treatment, they experience considerable sickness and discomfort, and their productivity is reduced. If treatment does occur, it typically involves antibiotics, and this often cures the infection. Although usually effective, antibiotics are not always ideal. Decades of their overuse has led to many bacteria that are resistant to antibiotics and, thus, as time goes on, antibiotics become less and less effective. Furthermore, there exists a diverse microbiota within each person s gut, and these microbes are essential for proper digestion and immune function. Antibiotics can wreak havoc on these beneficial microbial communities, enabling pathogenic species to invade and cause problems. Therefore, it would be ideal if military personnel could be treated for diarrhea-causing infections using a treatment other than antibiotics. The objective of the proposed research is to develop such treatments that are based on small viruses that infect only bacteria, i.e., are completely harmless to humans. These viruses, known as bacteriophages, or simply "phages," are incredibly diverse and typically only infect one strain or species of bacteria. Therefore, treatments based on phages would not eliminate the beneficial bacteria, only the targeted pathogenic bacteria. Phage therapies have enormous potential to ease the burden of antibiotic resistance, but have been limited in the past due in part to the difficulty of identifying which phages would be best for therapy. Because phages differ in their ability to kill the bacterial target, their stability in the absence of bacteria, and their likelihood of becoming ineffective due to bacterial resistance, it is important to rigorously study multiple phages in order to identify those with therapeutic potential. Phages are the most numerous and diverse biological entities on the planet, but no one can see them and they cannot live without their bacterial hosts, so discovering and studying them is very time-consuming and difficult. To do this, the research approach described herein relies on the creation of a robotics platform that can search through hundreds of environmental samples each day to isolate phages that already exist and that naturally seek and kill the bacteria to be eliminated from the human body. Once numerous phages are discovered, cutting-edge tools and technology are used to study each phage s ability to efficiently kill its bacterial target and whether that bacterial target can easily develop resistance to the phage. The resultant information is then used to engineer mixtures of phages, known as "phage cocktails," for preventing or treating diarrhea. It is this "smart" design of phage cocktails that sets the proposed research ahead of others pursuing phage therapy. Phage cocktails can also be further optimized to be stable under a variety of conditions, to enable their long-term storage under the extreme environmental conditions often experienced by the military when abroad. Options for treatment include preventative, where individuals could take a dose regularly to prevent infection, or acute therapy, where individuals suffering from diarrhea could take a dose in order to be cured.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710161
Entities
People
- Anika Kinkhabwala
Organizations
- United States Army