Identification of genes that differentiate Mannheimia haemolytica genotypes 1 and 2 using a pangenome approach

Mannheimia haemolytica is an opportunistic bacterial pathogen associated with the economically costly bovine respiratory disease. Two genotypes have been described, of which genotype 2 is more strongly associated with disease. Several previous studies have investigated the genomic differences between the genotypes and/or the major serotypes (1, 2 and 6) of M. haemolytica, however we still lack a clear basis for the greater disease association of genotype 2 (serotypes 1 and 6) and demonstrations of phenotypic differences are scarce. This work builds upon previous investigations to identify genes that differentiate the two genotypes with a particular focus on genes that may play a role in virulence and fitness in the respiratory tract microbiome. We identified 422 genotype differentiating genes in a collection of 206 unique M. haemolytica genomes (61 genotype 1, 145 genotype 2). Genotype differentiating genes included genotype-associated variants of a TonB-dependent siderophore receptor homolog, transferrin binding protein B, leukotoxin A, and IgA1 proteases. We also identified a genotype 1 associated lytic transglycosylase, and a genotype 2 specific highly immunogenic outer membrane lipoprotein. Genotype 2 genomes were significantly larger in size and contained more predicted protein coding genes than genotype 1 genomes. These results expand our knowledge of what differentiates the genotypes 1 and 2 of M. haemolytica and provides information that can be used as the basis for laboratory investigations of corresponding phenotypic differences.