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

Lawrence Broxmeyer, Danuta Sosnowska, Elizabeth Miltner, Ofelia Chacoón, Dirk Wagner, Jeffery Mc Garvey, Rauúl G. Barletta, Luiz E. Bermudez

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1155-1160
Number of pages6
JournalJournal of Infectious Diseases
Volume186
Issue number8
DOIs
StatePublished - Oct 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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