Disarming the most dangerous of superbugs

Zebrafish embryos show a 'hot spot' of neutrophils happening when
the specific bacterial metabolic pathway is blocked. Those neutrophils
then eliminate the bacteria very quickly.  Image:
www.pnas.org/content/early/2016/08/08/1523116113

Among the six most deadly antibiotic-resistant bacteria in the world, Acinetobacter baumannii targets the sick and elderly in hospitals. Now, researchers from Monash University have uncovered a way to effectively turn the patient’s immune system into an assassin against this lethal invader.

Led by Professor Anton Peleg, head of the Department of Infectious Diseases in Monash’s Central Clinical School and lab leader in the Biomedicine Discovery Institute, the research team developed a zebrafish model which allows scientists to study real-time interactions between immune cells and the deadly bacteria A. baumannii during infection.

Professor Peleg said the research, published over the weekend in the Proceedings of the National Academy of Sciences (PNAS), identified a bacterial metabolic pathway that, when inhibited, leads to an enhanced immune response towards the bacteria.

“Not only did we achieve improved bacterial clearance, we reduced the severity of the disease,” Professor Peleg said.

“These results pave the way for novel therapeutic targeting of bacterial metabolism to stimulate immune responses to fight off infection.”

The researchers focused on the zebrafish model because they discovered that the immune response to the bacteria in the fish was highly conserved with that in humans.

“Zebrafish are transparent so we could literally watch the way the bacteria caused a lethal infection and how the immune response reacted, which provides us with insights of what could happen in patients,” Professor Peleg said.

They identified a unique bacterial trigger of the immune pathway which, when activated, fought off the infection. While this opens a completely new avenue for treating these infections, Professor Peleg added that it is important because “it’s not just developing another antibiotic, in this case we are able to trigger the patient’s immune system to fight off the infection.”

Reference: Md Saruar Bhuiyana, Felix Ellett, Mohd Hafidz Mahamad Maifiah, Gerald L. Murray, Xenia Kostoulias, Gustavo M. Cerqueira, Keith E. Schulze, Jian Li, Darren J. Creek, Graham J. Lieschke, and Anton Y. Peleg. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis. PNAS doi: 10.1073/pnas.1523116113

01/09/2016 Herald Sun story