Mycoplasma gallisepticum is a respiratory and reproductive tract pathogen of poultry, and disease results in major economic losses on commercial farms worldwide. M. gallisepticum can be transmitted via inhalation of aerosolized respiratory secretions and can also be spread vertically to the offspring of infected hens. Infected chickens are at increased risk of developing a more severe, and potentially fatal, polymicrobial disease known as chronic respiratory disease (CRD). 

Elucidation of the mechanisms by which M. gallisepticum exerts its virulence on its host is critical for the rational pursuit of improved vaccines and control strategies. 

Research to date has resulted in the discovery of numerous virulence, or virulence-associated, determinants, that play significant roles in the pathogenic process. Attachment to the respiratory epithelium is the initial and most critical event leading to host colonization and disease. This is mediated by the primary and accessory cytadhesin molecules, GapA and CrmA, respectively. M. gallisepticum also binds host extracellular matrix molecules, which potentially aids in its attachment during infection and dissemination throughout the host. Surface exposed molecules such as PlpA and Hlp3 bind fibronectin and the OsmC-like protein has been shown to bind heparin. The OsmC-like protein also confers organic hydroperoxide resistance for M. gallisepticum in the extracellular milieu and may be essential for survival in the host. Numerous lipoproteins encoded by the vlhA gene family have been shown to mediate phase variation on the bacterial surface and are believed to be involved in evasion of the host immune system, contributing greatly to the chronicity of the disease. Metabolic pathways have also been shown to contribute to M. gallisepticum virulence. Dihydrolipoamide dehydrogenase (Lpd), a component of the pyruvate dehydrogenase complex, has been shown to be required for in vivo growth and survival in the host. Recent data indicates that, malF, a predicted ABC sugar transport permease, may be essential for M. gallisepticum persistence in birds. Collectively these factors appear to function in synergy to effect optimal colonization, sustainability and virulence.

In 1994 Mycoplasma gallisepticum was first recognized as an emergent pathogen of the American house finch (Carpodacus mexicanus), which appears to have jumped host species and tissue specificity (respiratory and reproductive tissues vs. conjunctiva). Poultry isolates do not cause disease in house finch and house finch isolates do not cause disease in poultry. M. gallisepticum from house finch (MGHF) represent a monophyletic clade relative to sequenced poultry isolates, with genomic changes indicating a novel M. gallisepticum lineage. The most dramatic differences among HFMG isolates involved the VlhA lipoproteins, indicating that they likely play an important role at the interface between pathogen virulence and host immunity.