NO molecules, and they have a wider range of functions.

To defend themselves, bacteria deploy an army of small thiol mops that sop up the SNO barrage and then break SNO down into harmless compounds.This is a bacterium's first line of defense.

If too much SNO gets in, it disables the bacteria by damaging key proteins the bacteria need to survive. While the bacteria are busy trying to repair themselves, the macrophages can attack and destroy them.

But the scientists discovered that the bacteria have an additional defense system. SNO compounds also attach to a transcription factor, a protein that finds specific genes on the bacterial genome and activates them. The genes, in turn, are translated into proteins whose job it is to break down the excess SNO, rendering it harmless.

In this way, bacteria have evolved an ingenious second line of defense against an SNO attack, Stamler said in an interview. "The bacteria offer SNO a target, which turns out to be a genetic switch that leads to its own destruction." he said. "The moment SNO enters a bacterium, a race is on as to whether it will defend itself quickly enough to evade the immune attack, or whether the SNO will win by quickly disabling the cell, making it vulnerable to a macrophage attack. In some cases, then, the bacterium wins, forming resistance to an immune system attack."

The findings offer both practical and profound implications, Stamler said.

The immediate benefit of the research is to suggest a way that new antibiotic drugs might be developed, said Hausladen, the study's first author. These drugs could plug up the transcription factor, known as OxyR, preventing it from being switched on, or they could bind to and deactivate the proteins that are produced to break down SNO. "This would be a novel way to disarm bacteria that has never been exploited,
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Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University Medical Center
14-Aug-1996


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