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The human pathogen Tropheryma whipplei is the only known reduced genome species (<1 Mb) among the Actinobacteria [high guanine-plus-cytosine (G+C) content Gram-positive bacteria]. Here we report the sequence of its small 927,303 base pair circular genome. While the G+C content is a surprisingly low 46%, 552 of the 808 identified ORFs have their closest homologues (less than 50% identical residues on average) within other actinobacteria genomes, confirming the prior classification of T. whipplei within the high G+C class. Despite its small size, the genome of T. whipplei remains well equipped in metabolic activities, except for deficiencies in the biosynthetic pathways of 10 amino acids, and the surprising lack of clear thioredoxin and thioredoxin reductase gene homologues. T. whipplei resistance to quinolone antibiotic correlates with a mutation in DNA gyrase. The analysis of the genome sequence of T. whipplei, on which so little was previously known, immediately guided the development of an axenic medium for its culture and identified repeated sequence target for improving its molecular diagnostic. |