Navigation Links
UC Davis researchers discover molecular target for the bacterial infection brucellosis

(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 because antibiotic therapy was not used during the acute, or early, phase of the infection," said Tsolis.

Tsolis and her collaborators were the first to discover PPARγ's role in brucellosis and to determine that AAMs harbor the bacteria during the chronic stage of the disease. The identification of the bacteria's niche is another important clue for the development of a more effective treatment, she said.

In a series of experiments, Tsolis and collaborators found that the gene encoding PPARγ is very active during chronic Brucellosis infection, but not during acute infection, and that the B. abortus bacteria did not survive in AAMs when deprived of glucose.

When the researchers inactivated the protein that normally transports glucose, the bacteria stopped reproducing, and the infection no longer was chronic, she said.

In mice infected with B. abortus, Tsolis and collaborators treated the animals with GW9662, a PPAR inhibitor. The researchers administered the inhibitor before the infection became chronic, or long lasting. The inhibitor significantly reduced the amount of AAMs and B. abortus bacteria in the mice.

"These results suggested that inhibition of PPARreduced the bacteria's survival by reducing the abundance of AAMs during chronic infection," said Tsolis.

Conversely, when the researchers treated the B. abortus-infected mice with Rosiglitazone, a drug that boosts PPAR activity, the bacteria increased by two-fold during the acute phase and four-fold during the chronic phase of infection. Rosiglitazone and other drugs that boost PPARare used to treat type 2 diabetes because they lower blood glucose by increasing cellular glucose uptake.

In other experiments, the researchers showed that AAMs, one of two categories of macrophages, are abundant in the spleen during chronic brucellosis but not during the acute, or initial, phase of the infection, which is dominated by classically activated macrophages (CAM), the second category of these immune cells.

In addition to profuse sweating, symptoms of brucellosis infection include joint and muscle pain. Among the complications of chronic infection are arthritis and endocarditis, a serious inflammation of one of the four heart valves. Brucellosis rarely occurs in the U.S., with about 100 to 200 cases reported each year, according to the U.S. Centers for Disease Control and Prevention.


Contact: Carole Gan
University of California - Davis Health System

Related biology news :

1. UC Davis study deflates notion that pear-shaped bodies more healthy than apples
2. UC Davis researchers aid effort to sequence the complex wheat genome
3. UC Davis researchers develop new drug delivery system for bladder cancer using nanoparticles
4. UC Davis study finds that above-normal weight alone does not increase the short-term risk of death
5. UC Davis scientists find new role for P53 genetic mutation -- initiation of prostate cancer
6. Researchers report a critical role for the complement system in early macular degeneration
7. Researchers study seleniums effects on horses
8. Researchers discover protein that helps plants tolerate drought, flooding, other stresses
9. Fresh analysis of dinosaur skulls by penn researchers finds 3 species are 1
10. HSCI researchers extend human epigenomic map
11. Researchers re-evaluate swine nutrition
Post Your Comments:
(Date:11/16/2015)... , Nov 16, 2015  Synaptics Inc. (NASDAQ: ... interface solutions, today announced expansion of its TDDI ... touch controller and display driver integration (TDDI) ... smartphones. These new TDDI products add to the ... resolution), TD4302 (WQHD resolution), and TD4322 (FHD resolution) ...
(Date:11/12/2015)... 2015   Growing need for low-cost, easy ... been paving the way for use of biochemical ... analytes in clinical, agricultural, environmental, food and defense ... in medical applications, however, their adoption is increasing ... continuous emphasis on improving product quality and growing ...
(Date:11/10/2015)... 10, 2015 About signature ... helps to identify and verify the identity of ... as the secure and accurate method of authentication ... particular individual because each individual,s signature is highly ... when dynamic signature of an individual is compared ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... 27, 2015 ... of companion diagnostics is one of the ... with pharmaceutical companies and diagnostic manufacturers working ... . --> ... on global cancer biomarkers market spread across ...
(Date:11/25/2015)... India , November 26, 2015 ... The Global Biobanking Market 2016 - 2020 report ... by maintaining integrity and quality in long-term samples, ... enabling long-term cost-effectiveness. Automation minimizes manual errors such ... the technical efficiency. Further, it plays a vital ...
(Date:11/25/2015)... BRUSSELS , November 25, 2015 ... in cat and human plaque and pave the way for ... health problems in cats     ... the most commonly diagnosed health problems in cats, yet relatively ... until now. Two collaborative studies have been conducted by researchers ...
(Date:11/25/2015)... 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS; TSX: ... prospects remain fundamentally strong and highlights the following ... received DSMB recommendation to continue the ZoptEC Phase ... the final interim efficacy and safety data ... men with heavily pretreated castration- and Taxane-resistant prostate ...
Breaking Biology Technology: