April 23, 2008
The global tuberculosis (TB) epidemic is in enormous need of newer ways to combat the disease. Each year, 9 million people develop TB and about 2 million die. Newer drug resistant and multi-drug resistant strains are complicating treatment efforts worldwide, especially in resource-poor nations and when combined with treating HIV disease. Now, results from a recent British study looking at how tuberculosis (TB) survives during transmission have uncovered "fat and lazy" bacteria, which may present a new avenue for prevention and treatment.
This study built upon a separate recent observation that some TB cells contain a substance called triacylglycerol synthase that is found in TB bacteria as they enter a very slow or non-replication state in their life cycle. The researchers set out to investigate the phenomenon further in newly diagnosed people. Samples of mucous from the lungs (sputum) of untreated people in the United Kingdom and Gambia were examined for the presence of lipid bodies and compared to TB samples grown in the lab. Over time, the lab samples were exposed to different stressors, such as a lack of oxygen, to find out how the TB responded.
The reason for the "fat" remark directed at this very slow or non-replicating TB is due to discovering lipid bodies containing the fat triacylglycerol within the cells. More triacylglycerol built up as the lab cultures were continually stressed during this state. The more stress that TB encountered, the more fat that accrued and the slower it replicated. This phenomenon may also apply to TB being stressed from anti-TB drugs, though this study did not evaluate that.
What appears to be happening is that one of TB's survival techniques is to build up fat and slow down its replication cycle. Stressors -- like its access to less oxygen or other factors present -- force TB into a slow state of replication. The researchers concluded that TB may need to enter this state of "fatty laziness" in order to survive during transmission and infection. This is likely also a reason why TB is so persistent and difficult to treat. A normal course of treatment lasts six months, while some people need longer courses.
Not much is known about this persistent non-replicating part of TB's life cycle. It has been generally accepted that sputum contains rapidly growing bacteria that are released from infected areas of the lungs. Yet these results show that fat and lazy TB bacteria actually outweigh active TB in sputum. Finding these populations of fat and lazy TB in all the sputum samples presents new considerations for changing how the disease is treated.
Treatments for TB have remained static for decades, so finding new avenues to stop TB transmission and infection have become critically important. The results from this study may provide researchers new targets to exploit the components of these TB "couch potatoes". Drugs could then be designed to interfere with this cycle, ultimately finding new ways to treat and perhaps cure TB infection and disease. At the least, treating TB in this fat and lazy state might reduce the burden that people face by having to take six months of drugs.