Elizabeth Amarh- Hatfull Lab
Investigaing genomic adaptations in non-tuberculous mycobacteria (NTM) and mycobacteriophages
Non-tuberculous mycobacteria (NTM) are species of mycobacteria that do not cause
tuberculosis. NTM are common causes of infections in immunocompromised individuals, and
are often highly antibiotic resistant. Antibiotic resistance in these infections necessitates an
alternative therapy to treat these infections, such as phage therapy. I am interested in
understanding what makes for a successful NTM and phage combination for applications in
phage therapy. To this end, I have surveyed a series of NTM strains to determine variations in
the patterns of phage susceptibilities of members of the MAB and MAC complexes. Overall,
there is great variation in phage infection, and many strains are not susceptible to any of the
tested phages. Two strains of M. abscessus subsp. bolletti are the most susceptible and are
infected by 36% of the phages surveyed. Similarly, while 80% of M. avium are not susceptible to
infection by the phages tested, one strain is susceptible to multiple phages of differing genomic
clusters, while four others are susceptible to 1-2 phages tested. Overall, the phage susceptibility
profiles are highly varied and unpredictable, and are not necessarily correlative with the genomic
relationships of the NTM strains. There are likely to be numerous explanations for these
susceptibility profiles, including surface differences influencing absorption and DNA injection,
as well as cytoplasmic systems promoting abortive infection or direct interference with phage
growth. Preliminary data with control strain mc2155 supports that it is possible to determine the
stage of lytic growth that is inhibited by the MAB and MAC strains when susceptibility to phage
infection is not observed. Because many NTM strains carry one or more prophages in their
genomes – and possibly prophage remnants that are challenging to bioinformatically identify –
prophage-mediated heterotypic viral defense systems could play substantial roles in determining
the phage susceptibility profiles. 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, September 11, 2020
12 PM
A219B or via Zoom