The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis

We have undertaken the inventory and assembly of the typical subunits of th e ABC transporters encoded by the complete genome of Mycobacterium tubercul osis. These subunits, i.e. the nucleotide binding domains (NBDs), the membr ane-spanning domains (MSDs) and the substrate binding proteins (SBPs), were identified on the basis of their characteristic stretches of amino acids a nd/or conserved structure. A total of 45 NBDs present in 38 proteins, of 47 MSDs present in 44 proteins and of 15 SBPs were found to be encoded by nf, tuberculosis. Analysis of transcriptional clusters and searches of homolog y between the identified subunits of the transporters and proteins characte rized in other organisms allowed the reconstitution of at least 26 complete (including at least one NBD and one MSD) and 11 incomplete ABC transporter s. Sixteen of them were unambiguously classified as importers whereas 21 we re presumed to be exporters. By searches of homology with already known tra nsporters from other organisms, potential substrates (peptides, macrolides, carbohydrates, multidrugs, antibiotics, iron, anions) could be attributed to 30 of the ABC transporters identified in AL tuberculosis. The ABC transp orters have been further classified in nine different sub-families accordin g to a tree obtained from the clustering of their NBDs. Contrary to Escheri chia coli and similarly to Bacillus subtilis, there is an equal representat ion of extruders and importers. Many exporters were found to be potentially implicated in the transport of drugs, probably contributing to the resista nce of M. tuberculosis to many antibiotics. Interestingly, a transporter (a bsent in E. coli and in B. subtilis) potentially implicated in the export o f a factor required For the bacterial attachment to the eukaryotic host cel ls was also identified. In comparison to E. toll and B. subtilis, there is an under-representation of the importers (with the exception of the phospha te importers) in M. tuberculosis. This may reflect the capacity of this bac terium to synthesize many essential compounds and to glow in the presence o f few external nutrients. The genes encoding the ABC transporters occupy ab out 2.5% of the genome of M. tuberculosis. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights re served.