(SACRAMENTO, Calif.) UC Davis scientists have uncovered a potential drug target for the development of an effective therapy against the debilitating, chronic form of the bacterial disease brucellosis, which primarily afflicts people in Mediterranean and Middle Eastern countries.
Brucellosis, which affects about 500,000 people worldwide each year, typically is caused by ingestion of unsterilized milk or close contact with body secretions from infected animals. Symptoms include intermittent or irregular fever of variable duration, headache, weakness, profuse sweating, chills, weight loss and generalized aching. It can also cause long-lasting or chronic symptoms such as recurrent fevers, joint pain and fatigue.
In a paper published online this week in the journal Cell Host & Microbe, the researchers reported that they have identified the cells that harbor the B. abortus bacteria during the persistent phase of the brucellosis. The cells, known as alternatively activated macrophages (AAMs), are a recently identified category of immune defense cells.
The researchers also determined that the biological pathway peroxisome proliferator activated receptor γ, abbreviated as PPARγ, is responsible for altering the metabolism of AAMs so that they supply B. abortus with the energy in the form of glucose that enables bacteria to survive and replicate and thereby sustain the chronic phase of the infectious disease. Other labs also have shown that PPARγ control a cell's metabolism.
"We found that PPARγ induces a metabolic shift in these cells that causes them to generate glucose," said Renee Tsolis, associate professor of medical microbiology and immunology at UC Davis who led the study.
"Starving the B. abortus bacteria by inhibiting the PPARγ pathway may be a new approach to eradicating the chronic, difficult-to-treat form of Brucellosis infection that usually occurs becaus
|Contact: Carole Gan|
University of California - Davis Health System