Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens.

TitleKilling of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens.
Publication TypeJournal Article
Year of Publication2002
AuthorsBroxmeyer L, Sosnowska D, Miltner E, Chacón O, Wagner D, McGarvey J, Barletta RG, Bermudez LE
JournalThe Journal of infectious diseases
Volume186
Issue8
Pagination1155-60
Date Published2002 Oct 15
ISSN0022-1899
KeywordsAnimals, Cell Line, Macrophages, Peritoneal, Membrane Fusion, Mice, Mycobacteriophages, Mycobacterium avium, Mycobacterium smegmatis, Mycobacterium tuberculosis, Phagosomes, Time Factors, Tuberculosis
Abstract

Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency 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.

DOI10.1086/343812
Alternate JournalJ. Infect. Dis.