Lawrence Broxmeyer, M.D.

Med-America Research

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TB & Outbreaks Week - October 22, 2002 - Page 9

Novel phage-based treatment effective against mycobacterial infections

2002 OCT 22 - ( -- by Michael Greer, senior medical writer - Researchers in the United States have developed a novel technique for fighting tuberculosis and other mycobacterial infections.

While effective treatment options are already available for afflicted patients, standard
antimicrobial agents are "limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms," according to Lawrence Broxmeyer and colleagues at Med-America Research in Whitestone, New York and other institutions in California, Nebraska, and Texas.

To overcome these problems, nonpathogenic mycobacteria could be used to deliver
bacteriophage viruses to attack infected cells, Broxmeyer and coauthors argued.
The researchers assessed the antimicrobial efficacy of Mycobacterium smegmatis organisms carrying the lytic TM4 phage virus, introducing these virus-laden microbes into tuberculosisinfected macrophage cultures. The amount of viable intracellular pathogens dropped significantly after phage treatment, according to the report.

Similar results were seen in cultures of cells infected with M. avium, study data showed. This
organism is responsible for life-threatening opportunistic infections in HIV/AIDS patients although it is generally harmless in people with normal immune function.

TM4-induced reductions in bacilli levels were both time- and dose-dependent (Killing of
Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens.

Journal of Infectious Diseases, October 15, 2002;186(8):1155-1160).

"These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development," Broxmeyer and colleagues concluded.

The corresponding author for this report is Luiz E. Bermudez, Department of Biomedical
Sciences, College of Veterinary Medicine, Oregon State University, Corvalus, OR 97331, USA.


Key points reported in this study include:
• A novel phage-based treatment can kill Mycobacterium tuberculosis and related
• This technique uses nonvirulent M. smegmatis loaded with TM4, a lytic
bacteriophage virus
• TB-infected macrophage cultures showed significant drops in bacilli levels after
• Similar results were seen in cultures infected with M. avium, which causes lifethreatening
opportunistic infections in HIV/AIDS patients

This article was prepared by TB & Outbreaks Week editors from staff and other reports.
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