Under the lens
Mycobacteria make daunting subjects for study. In contrast to the more commonly used organism for molecular biological research, the E Coli, which produces a visible colony in about eight hours, Mycobacterium tuberculosis requires three to four weeks to yield a comparable colony. Its formidable waxy coat of multiple complex lipids and carbohydrates renders it impermeable to many drugs. Because of its pathogenicity and transmission by aerosols, current biosafety regulations require that work with M tuberculosis be carried out under expensive biological containment. Hence, research on the pathogen is slow and demanding.
Although the study of microbial genetics developed over 40 years ago, little beyond the size of the M tuberculosis' genome and DNA content was known. In the last five years, methods that enable gene transfer in mycobacteria and selection for recombinants that contain introduced genes and permit the expression of foreign genes, have been developed.
Individual strains of M tuberculosis have shown several repetitive DNA elements with distinct banding patterns in DNA fingerprinting analysis. Multiple isolates from different patients exhibiting the same DNA fingerprint pattern suggest that each derives from a common source. This molecular epidemiology can be used to track sources of infection and transmission of individual strains. including drug- resistant ones. The common diagnostic methods for TB require two to eight weeks. With the use of M tuberculosis specific repetitive or single-copy sequences. polymerase chain reaction could provide diagnosis in a few hours.
Although virulent genes of M tuberculosis exist. the nature of mutation is unknown. Not a single gene involved in the pathogenesis of TB has been defined. Nor has the mechanism of resistance to any drug been identified; no new mycobacterial target for drug development has been characterised in 20 years.
Nonetheless. it is gratifying to note that the Human Genome Project which did not initially entertain proposals on any human pathogens. has recently included M tuberculosis and M leprae in its ambit. With appropriate support. the entire DNA sequence of these pathogens should be known in three to five years -a farsighted scientific investment indeed.
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