Elizabeth Amarh - Hatfull Lab
Prophage profiles of non-tuberculous mycobacteria
Non-tuberculous mycobacteria (NTM) are species of mycobacteria that do not cause tuberculosis. There are many species and subspecies of mycobacteria, with some of the most pathogenic belonging to the Mycobacterium abscessus (MAB) complex. Infections with NTM are problematic for those with cystic fibrosis and those with compromised immune systems. Treatment of these infections with antibiotics is challenging, as many MAB strains are intrinsically drug resistant (MDR), and non-responsive to antibiotic treatment. The therapeutic use of bacteriophages present an alternative potential therapy. Recent results from therapeutic application of phage in MDR NTM cases show strong safety profiles and clinical improvements for many patients. One of the challenges these cases have been met with is the limited number of phages able to successfully infect and kill these strains (< 10 phages). Additionally, current methods for identifying phages with therapeutic potential can be time consuming. If it could be possible to predict a strain’s susceptibility to phage infection, therapeutic phage isolation can be expedited. Among the many plausible explanations for these susceptibility dynamics, from receptors to post-injection systems promoting abortive infection, are prophages. In seeking to understand what influences a strain’s susceptibility to phage infection, I have analyzed the genomes of over 20 clinically isolated M. abscessus strains. From 14 of the strains (70%), 25 complete prophage sequences were identified. Of these 25 prophages, prophiEA01-1 and prophiBWHD-1 have been described previously (prophiATCC19977-1 and prophiGD04-1 respectively). Prophages prophiT46-3 and prophiT45-2 were isolated from two different strains, T46 and T45 respectively, and are identical. Similarly, prophages prophiBWHA-1 and prophiBWHB-1 were isolated from two different strains and are identical. Strains T45 and BWH- C contain nearly complete prophages, and this is likely a consequence of the disconnected contigs that result from whole genome sequencing. One of these incomplete prophages in T45 has been described in phage form as phiT45-1; while the complete prophage prophiT46-1 has been described in phage form as phiT46-1. All strains contain prophage segments, ranging from 6300 ~ 47,000 bases, interrupted by contig-breaks. Interestingly, one long prophage-like region was identified from three different strains, and appears to be two prophages integrated at the same attB site in the host genome. Elucidating the basis of phage susceptibility and the role of prophage-mediated defenses is a critical step in advancing the therapeutic potential of bacteriophages for treating antibiotic resistant NTM infections.
Friday, November 12th, 2021
A219B Langley Hall
12:00 PM