TB bacteria fatten up to survive
03 April 2008
One of the biggest hurdles to controlling TB is that the bacterium responsible (Mycobacterium tuberculosis) is very efficient at spreading from one person to another. Despite this, little is known about the transmission of this bacterium.
Now, researchers from the University of Leicester, St George’s, University of London and the MRC laboratories in The Gambia, have revealed some key characteristics of M. tuberculosis as it spreads between people. This work increases our understanding of this part of the bacterium’s life cycle, and could ultimately help researchers identify new targets to prevent and treat TB, which claims the lives of two million people each year.
The research team, led by Professor Mike Barer from the University of Leicester, studied sputum samples collected from patients with TB in the UK and The Gambia. The researchers found that a proportion of the M. tuberculosis cells in all samples contained small, fat-filled structures, absent from bacteria grown in the lab. They also found that these ‘fatty’ bacteria were in a non-replicating state. According to the researchers, being ‘fat and lazy’ helps the bacteria survive as they pass from one person to another.
Professor Philip Butcher and colleagues from St George’s used whole-genome microarrays (gene chips) to study the gene expression patterns of the bacteria in sputum. The microarrays, based on the genome sequence of M. tuberculosis assembled at the Wellcome Trust Sanger Institute, were made available through the Trust-funded Bacterial Microarray Group at St George’s.
The results showed that sputum-derived bacteria have ‘switched on’ genes responsible for cholesterol metabolism, suggesting cholesterol could be a nutrient source for the bacteria while in the liquefying and necrotic lung tissue found in TB.
In another part of the study, the researchers grew TB bacteria in the lab under low oxygen levels, which causes the bacteria to enter a non-replicating persistent (NRP) state. In this state, the bacteria do not grow or replicate, and are not killed so effectively by antibiotics - they show drug tolerance.
Key similarities between NRP bacteria and those taken from infected sputum led the researchers to suggest that the a proportion of the TB bacteria in sputum are in an inactive, NRP-like state. This goes against established thinking that M. tuberculosis released from the infected lungs into the sputum is rapidly multiplying, and could explain why patients need an extended course of antibiotics to completely clear TB.
Further work is needed to see if antibiotic treatment affects the proportion of ‘fat and lazy’ bacteria present, and to investigate if there is a link between these bacteria and a patient’s infectivity and response to treatment.
Image: Detail of an enhanced fluorescence image of a tubercle bacillus laden with fat droplets in a patient’s sputum; adapted from Microbiology-SGM 148:2002:2951-2958, with permission
References
Garton NJ et al. Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Med 2008;5(4)e75.
Cole ST et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;393(6685):537-44.