Deciphering the TB Bacterium Genome
Schematic of the TB bacterium's genome
Credit: The Institute for Genomic Research
TB isn't like a lot of other infectious diseases because Mycobacterium tuberculosis (Mtb) isn't like a lot of other microbes. In contrast to the mad dash of growth characteristic of many infectious agents, Mtb moves at a microbial snail's pace. It takes a full day for Mtb to complete a round of cell division, and 2 weeks of careful tending are required to grow visible quantities in the lab. This deliberate pace is matched by the slow progress of the disease. Frequently, active TB does not emerge until decades after the initial infection and the majority of infected people never develop the disease at all.
How does Mtb escape destruction by the immune system for so long? That question, and others related to details of Mtb's behavior in the human body, became a bit easier to address when the entire sequence of Mtb's genome was published in 1998. Scientist Stewart Cole and others at the Sanger Center in England determined the order of every base pair in Mtb's ring-shaped chromosome. The well-characterized laboratory strain of Mtb sequenced by the British scientists has a staggering 4.4 million base pairs—making it one of the largest microbial genomes yet sequenced.
In 1996, as the Sanger Center project was getting underway, NIAID issued a grant to U.S.-based The Institute for Genomic Research to determine the sequence of a different strain of Mtb. This highly virulent strain first infected a children's clothing factory worker and was dubbed "Oshkosh."
The 4.4 million base pairs of Mtb's genome comprise about 4,000 genes. By comparing the newly determined sequences with previously sequenced genes from other organisms, scientists can predict likely functions for about half of the genes. The other half have no counterparts among previously sequenced microbial DNA and may be unique to Mtb and its close relatives. Those 2,000 or so genes are now the subjects of intense scrutiny. Some must be responsible for Mtb's ability to evade the immune system, while others may give the organism its virulence. Still others probably code for proteins that help build Mtb's uniquely tough cell wall.
The wealth of information flowing from the genome sequencing projects electrified every aspect of TB research. With a host of new techniques, scientists are now able to gain their clearest view yet of this remarkable, and deadly, microbe.
References
Cole ST et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 393(6685):537-44 (1998).
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