Exploration of Lysogenic Phages as a Resource for Phage Therapy in Burkholderia pseudomallei-Induced Melioidosis
Pacharapong Khrongsee 1*, Thomas B. Walzek 1, Kuttichantran Subramaniam 1, Iris irby 1, Mariam Alami-Rose 1, Jedsada Kaewrakmuk 2, Apichai Tuanyok 1
- Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA 32608
- Faculty of medical technology, Prince of Songkla University, Hatyai, Songkhla, Thailand 90110
Pacharapong Khrongsee, firstpachar@ufl.edu
Burkholderia pseudomallei, a Gram-negative bacterium, is commonly found in tropical soils and freshwaters and is responsible for causing melioidosis in both humans and animals. Melioidosis poses significant challenges for animal treatment due to the emergence of antibiotic resistance, the prolonged and costly nature of effective antibiotic regimens lasting up to 20 weeks, and the complexities associated with decontaminating infected areas. As a result, bacteriophage (phage) therapy is being investigated as a possible treatment for this disease. We study lysogenic phages, the bacterial parasites that incorporate their genome into the host chromosome. We used bioinformatic tools to track the short direct repeat sequences at the 3'end of the recombination event in order to identify prophage regions in bacterial genomes sourced from the GenBank database. This method uncovered over 200 functional prophage regions distributed across 135 completed B. pseudomallei genomes. Ten recombination hotspots on B. pseudomallei chromosomes were discovered, with P2-like and Lambda-like bacteriophages being frequently observed. Many of these hotspots were found to be associated with tRNA gene sequences, specifically tRNA-phenylalanine, methionine, arginine, cysteine, serine, and selenocysteine. Transcriptomic analysis during normal bacterial growth revealed that the integrase gene play an important role in the phage lysogenic life cycle. Moreover, induction of the prophages resulted in the production of functional phages, thereby establishing a valuable resource for potential phage engineering strategies in future phage therapy applications targeting melioidosis.