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.