Location: Virus and Prion Research2012 Annual Report
1. Developed strategies to eliminate antibiotic resistant Staphylococcus bacteria in swine. Staphylococcus aureus (S. aureus) is an extremely common yet devastating human pathogen. S. aureus has an outstanding ability to acquire resistance to antibiotics, and in 2003, a new methicillin-resistant S. aureus (MRSA) lineage emerged associated with livestock species including pigs. Therefore the identification of factors or strategies to eliminate the presence of MRSA from swine herds is a top research priority for U.S. swine producers. Bacterial persistence is often linked to the development of microbial communities known as biofilms that make the bacteria resistant to immune responses, disinfectants, and antibiotics. ARS scientists at the National Animal Disease Center in Ames, Iowa determined that MRSA isolated from swine are capable of forming biofilms and found two compounds able to inhibit or disperse biofilm formation of these isolates. The rationale behind this approach is that compounds that can prevent or disperse biofilm formation will cause the bacteria to either revert to or be held in a free-living state where they are sensitive to host immune responses, disinfectants, available antimicrobial therapies, and other environmental pressures that lead to the clearance of the organism. Collectively, these findings provide a critical first step in designing strategies to control or eliminate MRSA in swine herds.
2. Determination of the genetic basis by which Haemophilus parasuis (H. parasuis) causes disease. H. parasuis is a bacterium that causes Glasser's disease in swine, a disease characterized by chronic debilitation and often death that costs the swine industry millions in losses annually. However, not all strains of the bacterium cause disease. To date, little is known about genetic differences among H. parasuis strains and the genetic factors that contribute to its ability to cause disease. ARS scientists at the National Animal Disease Center in Ames, Iowa determined the DNA genomic sequence of 10 strains of H. parasuis with varying capability of causing disease. The DNA sequence can now be used to compare the different isolates for identification of genes contributing to disease development. These data comprise the first publicly available genome sequence for this bacterium.
3. Virulence determinants of porcine reproductive and respiratory syndrome virus (PRRSV) are complex. Demonstrated the correlation of secondary bacterial infections in pigs infected with genetically varied isolates of PRRSV. PRRSV is one of the most devastating and costly diseases to the swine industry world-wide. PRRSV is ubiquitous and mutates rapidly making it difficult to develop vaccines that protect pigs from disease. ARS scientists at the National Animal Disease Center in Ames, Iowa determined the whole genomic sequence of 7 PRRSV isolates and found that the isolates varied considerably in their genomic sequence as well as their capacity to replicate in pigs and predispose to secondary bacterial pneumonia. No specific mutations correlated with disease, indicating specific genomic determinants of disease are complex. These experiments are elucidating mechanisms by which the virus causes disease and alters the pig's immune response to cause increased susceptibility to secondary bacterial infections.
4. Determined a mechanism by which porcine reproductive and respiratory syndrome virus (PRRSV) causes immunosuppression. PRRSV alters the pig's immune response to cause increased susceptibility to secondary bacterial infections. Neutrophils are cells of the immune system that play an important role in combating bacterial infection. Granulocyte-Colony Stimulating Factor (G-CSF), a compound normally produced by the body, increases the number of circulating neutrophils. The use of immunomodulators like G-CSF is a promising area for therapeutic and prophylactic use to prevent and combat infectious disease while eliminating or reducing the use of antibiotics. ARS scientists at the National Animal Disease Center in Ames, Iowa, completed a study in which pigs were given G-CSF to determine if it would reduce the incidence of secondary bacterial infections subsequent to PRRSV infection. Although G-CSF did not decrease the prevalence of secondary bacterial infections in PRRSV infected pigs, a paradoxical outcome of the viral infection was an abolition of the surge in circulating neutrophils created by G-CSF, which represents a previously unrecognized effect of PRRSV on the host immune system and may explain how PRRSV contributes to development of secondary bacterial infections.
Brockmeier, S.L., Loving, C.L., Nelson, E.A., Miller, L.C., Nicholson, T.L., Register, K.B., Grubman, M.J., Brough, D.E., Kehrli, Jr., M.E. 2012. The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus. Clinical and Vaccine Immunology. 19(4):508-514.