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

• Published in: The Journal of infectious diseases Vol. 186; no. 8; pp. 1155 - 1160
• Main Authors: Broxmeyer, Lawrence, Sosnowska, Danuta, Miltner, Elizabeth, Chacón, Ofelia, Wagner, Dirk, McGarvey, Jeffery, Barletta, Raúl G., Bermudez, Luiz E.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.10.2002; University of Chicago Press; Oxford University Press
• 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; Prognosis; Rodentia; Mycobacterium avium; Mycobacterium smegmatis; Myoviridae; Infection; Virus; T even phage; Vertebrata; Mammalia; Treatment; Mycobacterium tuberculosis; Mouse; Mycobacteriales; Follow up study; Animal; Mycobacteriaceae; Bacteria; Actinomycetes; Technique; Phage; Phage T4
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/343812

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