Lawrence Broxmeyer, Danuta Sosnowska, Elizabeth Miltner, Ofelia Chacon, Dirk Wagner, Jeffery McGarvey, Raul G. Barletta, and Luiz E. Bermudez
Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage
The Journal of Infectious Diseases
ABSTRACT
Mycobacterium avium causes disseminated infection in patients with acquired immune deficieny syndrome. Mycobacterium tuberculosis is a pathogen associated with the deaths of millions of people worldwide annually. Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. The present study describes a system using Mycobacterium smegmatis, an avirulent mycobacterium, to deliver the lytic phage TM4 where both M. avium and M. tuberculosis reside within macrophages. These results showed that treatment of M. avium–infected, as well as M. tuberculosis –infected, RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4, resulted in a significant time and titer dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fuses with the M. avium vacuole in macrophages. These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.
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