Tuesday, August 20, 2013

FAQ: Are there any new targets for treating bacterial infections?

Incidence of Brucella infections in animals during the first half
of 2006
(green-never reported; blue-not reported in this
period; brown-confirmed clinical disease; red-confirmed
infection; grey- no information

by Flukeman

In the case of the debilitating chronic form of the bacterial disease brucellosis, the answer is yes; according to a recent paper in Cell Host & Microbe. The paper entitled: 'PPAR-Mediated Increase in Glucose Availability Sustains Chronic Brucella abortus Infection in Alternatively Activated Macrophages' is the result of work by scientists at UC Davis. Brucellosis, which primarily affects people from the Mediterranean and Middle East, is typically the result of ingesting unsterilized milk or contacting the secretions of infected animals.

The paper reports that the scientists identified the cells that harbour B. abortus during persistent infection as a recently identified immune cell known as alternatively activated macrophages (AAMs). They also found that the metabolism of the AAMs is altered such that the B. abortus is supplied with glucose that allow for the survival of the bacteria and the resulting chronic infection.

This alteration in metabolism is induced by peroxisome proliferator activated receptor  (PPAR). PPAR now represents a target that can be inhibited thus starving the bacteria. As proof of principle the paper reports that treatment with a PPAR inhibitor significantly reduced AAMs and B. abortus in infected mice while treatment with a PPAR activator increased bacteria.