Preamble Two of the most important human pathogens are Mycobacterium tuberculosis, the etiologic agent of tu- berculosis, a chronic infectious disease that every year accounts for three million lives world-wide and M. le- prae, the causative organism of leprosy. Other myco- bacteria, in particular M. avium-intracellulare can cause disease in immuno-compromised individuals. Recent increases in tuberculosis cases in both devel- oping and industrialised countries, together with the emergence of potentially untreatable drug-resistant strains, have refocused the attention of scientists on the biology of these pathogens. One of the common fea- tures of the medically important mycobacteria is the considerable difficulty inherent in their manipulation in the laboratory. These pathogens have to be handled under biohazard-containment facilities, and are diffi- cult to cultivate. M. tuberculosis has a generation time of 24 hours in in vitro culture, whilst M. leprae cannot be cultivated at all on artificial media and has an ex- tremely long generation time of two weeks or more in experimentally infected animals. In addition mycobac- teria possess an exceptionally lipid-rich cell wall that Int. J. Med. Microbiol. 290, 143-152 (2000) © Urban & Fischer Verlag http://www.urbanfischer.de/journals/ijmm Comparative genomics of the mycobacteria Roland Brosch 1 , Stephen V. Gordon 1, 2 , Alexander Pym 1 , Karin Eiglmeier 1 , Thierry Garnier 1 , Stewart T. Cole 1 1 Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France 2 Present address: Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, England Received January 25, 2000 · Revision received January 31, 2000 · Accepted January 31, 2000 Abstract The genus mycobacteria includes two important human pathogens Mycobacterium tuberculosis and Mycobacterium lepra. The former is reputed to have the highest annual global mortality of all pathogens. Their slow growth, virulence for humans and particular physiology makes these organ- isms extremely difficult to work with. However the rapid development of mycobacterial genomics following the completion of the Mycobacterium tuberculosis genome sequence provides the basis for a powerful new approach for the understanding of these organisms. Five further genome sequencing projects of closely related mycobacterial species with differing host range, virulence for humans and physiology are underway. A comparative genomic analysis of these species has the po- tential to define the genetic basis of these phenotypes which will be invaluable for the development of urgently needed new vaccines and drugs. This minireview summarises the different techniques that have been employed to compare these genomes and gives an overview of the wealth of data that has already been generated by mycobacterial comparative genomics. Key words: comparative genomics – mycobacteria 1438-4221/00/290/2-143 $ 12.00/0 IJ IJMM Corresponding author: Roland Brosch, Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France, Phone: 33-1-45 68 84 49, Fax: 33-1-40 61 35 83, E-mail: rbrosch@pasteur.fr, http://www.pas- teur.fr/recherche/unites/Lgmb/