Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage Delivered by a Nonvirulent Mycobacterium: A Model for Phage Therapy of Intracellular Bacterial Pathogens

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 resistan...

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Bibliographic Details
Published in:The Journal of infectious diseases 2002-10, Vol.186 (8), p.1155-1160
Main Authors: Broxmeyer, Lawrence, Sosnowska, Danuta, Miltner, Elizabeth, Chacón, Ofelia, Wagner, Dirk, McGarvey, Jeffery, Barletta, Raúl G., Bermudez, Luiz E.
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacterial diseases
Bacterial sepsis
Bacteriophages
Biological and medical sciences
Cell Line
Human bacterial diseases
Infections
Infectious diseases
Macrophages
Macrophages, Peritoneal - microbiology
Major Articles
Medical sciences
Membrane Fusion
Mice
Mycobacteriophages
Mycobacteriophages - physiology
Mycobacterium
Mycobacterium avium
Mycobacterium avium - growth & development
Mycobacterium avium - virology
Mycobacterium avium complex
Mycobacterium smegmatis - physiology
Mycobacterium smegmatis - virology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - growth & development
Mycobacterium tuberculosis - virology
Phagosomes - microbiology
Time Factors
Tuberculosis - microbiology
Tuberculosis - therapy
Vacuoles
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Summary: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
ISSN:0022-1899
1537-6613
DOI:10.1086/343812