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Bacteriophages: The dark matter of the biosphere - 11 May 2021

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Speaker: Professor Graham Hatfull, Eberly Family Professor of Biotechnology, Department of Biological Sciences, University of Pittsburgh

Host: Mark Sanderson

The bacteriophage population is vast, dynamic, old, and not surprisingly massively diverse genetically. Comparative genomics of 3,000 sequenced phages infecting hosts within the phylum Actinobacteria shows they span a continuum of diversity but with unequal representation of the diversity landscape. This variation is driven by the complex dynamic interplay between the bacterial and phage populations with strong selection for bacterial survival under viral attack, and the need for phages to coevolve. Temperate bacteriophages are key players in this dynamic and carry prophage-expressed genes that confer defense against lytic phage infection, targeting both similar (homotypic) and dissimilar (heterotypic) phages. These complex relationships present a substantial challenge for the therapeutic application of bacteriophages, with high variation in phage susceptibility among clinical isolates of any given bacterial pathogen. Nonetheless, we have exploited the large collection of Actinobacteriophages to identify phages that infect and kill specific isolates of Mycobacterium abscessus, using a combination of newly evolved host ranges and genome engineering to promote efficient killing of the bacterial host. Therapeutic use of these phages illuminates their potential for control of highly antibiotic-resistant mycobacterial infections.   

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