Mycoplasma gallisepticum is a significant respiratory and reproductive pathogen of domestic poultry, responsible for considerable economic losses to the U S poultry industry. We conducted comparative genomic sequence analysis to identify genomic determinants of virulence and to elucidate genomic variability among strains of M. gallisepticum. Analysis of the high-passage, attenuated derivative of the virulent R(low) strain, R(high), indicated that relatively few total genomic changes (64 loci) occurred, yet they are potentially responsible for the observed attenuation of this strain. Further genomic analyses of the M. gallisepticum vaccine strain F revealed numerous differences relative to strain R(Low). Comparative genomic hybridizations indicated few genetic loci common to F and vaccine strains ts-11 and 6/85, which would correlate with proteins affecting strain R(Low) virulence. Collectively, these data provide novel insights into inter- and intrastrain M. gallisepticum genomic variability and the genetic basis of M. gallisepticum virulence, which have implications for rationale vaccine design.

In 1994 Mycoplasma gallisepticum was first recognized as an emergent pathogen of the American house finch (Carpodacus mexicanus).  To gain insights into the reason for this pathogen to have jumped host species and tissue specificity, we sequenced and compared the genomes of eight HFMG isolates, including the index isolate and seven others separated spatially and temporally (1994-2008) across the epizootic, and notably having differences in virulence. The most dramatic genomic differences among HFMG involved phase variable and immunodominant VlhA lipoprotein genes, including those variable in presence and genomic location. Overall, our data identify candidate virulence genes and reveal the importance of phase variable lipoproteins during evolution of M. gallisepticum emerging and disseminating in a novel host in nature, likely mediating an important role at the interface between pathogen virulence and host immunity.