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Immune system's distress signal tells bacteria when to strike back

stress, such as after major surgery ?let them know there's a problem."

For Pseudomonas, detecting interferon-gamma, "is like receiving a demolition notice from your landlord," Alverdy said. "It lets them know they need to find a new home. They don't take that news any better than we would."

A vulnerable host, like a condemned home, is a liability, a threat to its tenants' survival. Pseudomonas, however, has the tools to engineer its own escape ?by killing off the host.

This wily pathogen can evade a host's immune system. It can repel antibiotics, secrete toxins similar to those used by anthrax, latch onto the bowel wall, bore its way through, and flow into the blood stream. As a consequence, patients with widespread Pseudomonas infection often die within a few days.

Alverdy and colleagues were able to pinpoint key early steps of this lethal process. The transformation starts when a weakened host tries to boost its defenses against any possible invasion. The host's T cells release chemical signals that activate the immune system. One of those signals, interferon-gamma, is intercepted by a protein, called OprF, found on the outer membrane surface of Pseudomonas. This serves an early warning system.

Once Pseudomonas detects the first signs of a brewing immune response, they also begin to prepare for battle, gathering information and responding with their own counteroffensive.

Their first move is a process called quorum sensing, which bacteria use to gauge their own numbers. When interferon-gamma binds with OprF on the bacterial cell surface, it activates a gene called rhII. RhII triggers synthesis and secretion of a bacterial signaling molecule called C4-HSL. By measuring the amount of C4-SHL in their environment these bacteria can estimate their own numbers and density.

If they feel they are sufficiently numerous, they produce two virulence factors, molecular weapons known as PA-I and Pyocyanin. PA-I causes the
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Source:University of Chicago Medical Center


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