Edward Bernard, Samantha Jones, Joshua Kelley, Melody Neely
Mycobacterium abscessusis the leading cause of lung infection in cystic fibrosis patients and is often resistant to all antibiotics. There is an urgent need for alternative therapies such as lytic bacteriophage (viruses that infect bacteria). Phage therapy has been successful in the treatment of a drug-resistantM. abscessusinfection in a teenaged cystic fibrosis patient but there are challenges to broad use as most M. abscessusisolates are highly resistant to lytic bacteriophage infection. Prophage, or integrated bacteriophage genomes within the M. abscessusgenome, likely defend against phage superinfection via prophage-encoded viral defense systems. The Molloy lab has shown that the Mab cluster R prophage McProf increases bacterial resistance to both bacteriophage superinfection and antibiotics. To better understand the role of cluster R prophage in antibiotic resistance and superinfection immunity, we identified and characterized 25 novel cluster R genomes in sequenced clinical M. abscessusisolates. These strains encode a type VII secreted polymorphic toxin (PT) system that we hypothesize play a role in drug resistance and superinfection immunity. The PT cassettes include 1) a small ESXA-like protein, 2) a large PT with a N-terminus WXG100 motif and a C-terminus toxin domainand 3) a cognate immunity protein.There are two types of PT systems representedin the cluster R genomes: a Tde1-like DNAse and a second PT with no recognizable toxin motif. Promoter analysis of the MabR PT systems identified a poorly conserved putativeSigA promoter. To determine the role of PT in superinfection immunity and drug resistance, we attempted to clone and express the PT system from the MabR prophage prophiFSAT01-1 but were unable to isolate transformants in E. coli.
Archambault, Dakota, "Understanding the Role of Prophage Encoded Polymorphic Toxins in Mycobacterial Superinfection Immunity and Drug Resistance" (2021). Honors College. 643.