The Mycobacteria: a Postgenomic View

This chapter focuses on insights gained from genome exploration and functional analyses. It provides an overview of the evolution and of the infection strategies used by pathogenic mycobacteria and how this information may be useful for developing new insights into disease control. The importance of molecular characterization of Mycobacterium tuberculosis strains was also shown in a recent microarray analysis of a large number of epidemiologically well-defined M. tuberculosis isolates from San Francisco. One of the key findings of the sequence analysis was that M. tuberculosis differs radically from other bacteria in that approximately 10% of its coding capacity is dedicated to genes encoding proteins that are involved in lipid metabolism, both biosynthetic activities and lipolytic functions. The genes encoding the ATP binding cassette (ABC) transporters occupy about 2.5% of the genome of M. tuberculosis. These multi-subunit permeases, which transport various molecules like ions, amino acids, peptides, antibiotics, polysaccharides, and proteins across biological membranes, are classified as importers and exporters. The current bacillus Calmette-Guerin (BCG) vaccine is efficient in the protection against tuberculosis (TB) meningitis, but it often provides only minor protection against pulmonary TB, the prevalent form in adults. The availability of genome sequences from several mycobacterial species provides the principal resource for researchers to explore their pathogenic life cycle and evolution.