Friday, 29 November 2013

How Staph toxin disarms the immune system


Researchers at NYU Langone Medical Center have discovered a new mechanism by which the deadly Staphylococcus aureus bacteria attack and kill off immune cells. Their findings, published today in the journal Cell Host & Microbe, explain a critical survival tactic of a pathogen that causes more skin and heart infections than any other microbe.

Scientists have long known that Staph releases an arsenal of toxins to puncture immune cells and clear the way for infection. But only recently have they begun to understand exactly how these toxins work.

Earlier this year, researchers explained how one of those toxins, a protein called LukED, fatally lyses T-cells, macrophages and dendritic cells, all types of white blood cells that help fight off infection. The LukED toxin, they showed, binds to a surface receptor called CCR5 (the same one exploited by HIV).  But their discovery failed to explain how the bacterial toxin kills other types of white blood cells, such as neutrophils, that lack the CCR5 receptor.

Now some recent work solves this puzzle, showing for the first time how receptors on neutrophils (a common type of white blood cell) also enable binding of the LukED toxin. The researchers found that LukED latches onto surface receptors called CXCR1 and CXCR2, creating the same deadly pores that it does when it latches onto CCR5 receptors.

For further details, refer to the following paper:

Tamara Reyes-Robles, Francis Alonzo, Lina Kozhaya, D. Borden Lacy, Derya Unutmaz, Victor J. Torres. Staphylococcus aureus Leukotoxin ED Targets the Chemokine Receptors CXCR1 and CXCR2 to Kill Leukocytes and Promote Infection. Cell Host & Microbe, 2013; 14 (4): 453 DOI: 10.1016/j.chom.2013.09.005

Posted by Tim Sandle