Graham Hatfull

One third of the world’s people are infected with tuberculosis, and someone new is infected every second. TB is notoriously hard to treat, requiring a course of multiple antibiotics over six to nine months. Many people don’t complete the full course of treatment, which leads to increasing antibiotic resistance against the disease.

More effective treatments could be on the way, however, thanks to a new five-year, $2.8 million grant from the National Institutes of Health to Graham Hatfull, Eberly Family Professor of Biotechnology and chair of the Department of Biological Sciences in Pitt’s School of Arts and Sciences. William Jacobs, professor of microbiology and immunology at the Albert Einstein College of Medicine, is a key collaborator. Both Hatfull and Jacobs are supported by the Howard Hughes Medical Institute.

The key to better treating tuberculosis, they believe, may lie in a harmless cousin of TB called Mycobacterium smegmatis. In the cover story of the December 2005 issue of Cell, Hatfull and Jacobs described how M. smegmatis forms a drug-resistant coating called a biofilm.

The researchers made this discovery by infecting M. smegmatis with a bacteriophage nicknamed the “Bronx Bomber,” which Jacobs had isolated from his back yard, and which Hatfull has studied extensively. (Bacteriophages—“phages” for short—are viruses that infect bacteria.)

Hatfull and Jacobs found that when infected by the Bomber, the M. smegmatis germ could no longer form its protective coatings. This occurred because the phage had disrupted a M. smegmatis gene called groEL1—which has a nearly identical counterpart in M. tuberculosis.

The NIH grant will enable Hatfull and Jacobs to explore whether the Bomber also affects the groEL1 gene in the TB-causing germ. If so, it could pave the way for medications that similarly break down the bacteria’s defenses and thereby increase the effectiveness of antibiotics.

“We’d like to have an understanding of M. tuberculosis and what happens during an infection that leads to such difficult, prolonged treatment,” said Hatfull, who also codirects the Pittsburgh Bacteriophage Institute.

“An ideal scenario would be to develop drugs that would allow TB to be treated over a much shorter period of time,” he added. “Shortening the treatment would lead not only to more effective and simple control of the disease, but also would cut down on the development of drug-resistant organisms.”