The draft genome sequence of Mannheimia haemolytica A1, the causative agent of bovine respiratory disease complex (BRDC), is presented. Strain ATCC BAA-410, isolated from the lung of a calf with BRDC, was the DNA source. The annotated genome includes 2,839 coding sequences, 1,966 of which were assigned a function and 436 of which are unique to M. haemolytica. Through genome annotation many features of interest were identified, including bacteriophages and genes related to virulence, natural competence, and transcriptional regulation. In addition to previously described virulence factors, M. haemolytica encodes adhesins, including the filamentous hemagglutinin FhaB and two trimeric autotransporter adhesins. Two dual-function immunoglobulin-protease/adhesins are also present, as is a third immunoglobulin protease. Genes related to iron acquisition and drug resistance were identified and are likely important for survival in the host and virulence. Analysis of the genome indicates that M. haemolytica is naturally competent, as genes for natural competence and DNA uptake signal sequences (USS) are present. Comparison of competence loci and USS in other species in the family Pasteurellaceae indicates that M. haemolytica, Actinobacillus pleuropneumoniae, and Haemophilus ducreyi form a lineage distinct from other Pasteurellaceae. This observation was supported by a phylogenetic analysis using sequences of predicted housekeeping genes.Mannheimia haemolytica serotype A1 is the principle bacterial pathogen associated with bovine respiratory disease complex, also known as bovine shipping fever (25, 31). M. haemolytica resides in the upper respiratory tracts of healthy ruminants, although in immunocompromised animals, such as those with a preexisting viral infection, M. haemolytica can descend into the lungs, leading to pneumonia. The mortality and morbidity associated with this disease cause substantial losses to the cattle industry (25, 31). Hence, much research on M. haemolytica is directed at understanding its virulence and designing vaccines to protect cattle (31).M. haemolytica is a member of the family Pasteurellaceae, which is classified among the ␥-proteobacteria and includes human and animal pathogens of the genera Mannheimia, Pasteurella, Haemophilus, Actinobacillus, and Histophilus (31). M. haemolytica (formerly Pasteurella haemolytica) is classified in the genus Mannheimia based upon 16S rRNA sequence phylogeny and DNA-DNA hybridizations (3). The family Pasteurellaceae includes several members whose genomes have been sequenced: Haemophilus influenzae, Pasteurella multocida, Mannheimia succiniciproducens, Actinobacillus pleuropneumoniae, Histophilus somni, Haemophilus ducreyi, and Actinobacillus actinomycetemcomitans.The primary virulence factor of M. haemolytica is considered the leukotoxin. It is a calcium-dependent toxin that is a member of the RTX family of toxins. Cytolytic at low concentrations and apoptotic at high concentrations, the leukotoxin provokes an inflammatory response that can lead to intense ed...