Mannheimia haemolytica increases Mycoplasma bovis disease in a bovine experimental model of BRD.

Amongst the bacterial pathogens associated with the bovine respiratory disease syndrome (BRD) in cattle are Mannheimia haemolytica and Mycoplasma bovis. The interaction between these two pathogens has not been investigated before; thus, there are gaps in the knowledge of why and how a previous infection with M. haemolytica allows the development of M. bovis-related lesions. We hypothesized that upon M. haemolytica infection, inflammatory products are produced in the lung and that these inflammatory products stimulate M. bovis to produce proteases and lipases that degrade lipids and proteins important for lung function. In this work, we identified several M. bovis proteases and lipases whose expression was modulated by M. haemolytica products in vitro. We performed co-infection animal challenges to develop a model to test vaccine protection. A prior exposure to BHV-1 followed by infection with M. bovis and M. haemolytica resulted in severe pathology and the BHV-1 infection was abandoned. When M. bovis and M. haemolytica were introduced into the lungs by bronchoscopy, we found that M. haemolytica resulted in worsening of the respiratory disease caused by M. bovis. We performed a proof-of-concept trial where animals were immunized with the M. bovis proteins identified in this study and challenged with both pathogens. Despite detecting significant humoral immune responses to the antigens, the experimental vaccine failed to protect against M. bovis disease.