Exposure to hypochlorous acid causes bacterial proteins to unfold and stick to one another, leading to cell death. Image courtesy of the American Chemistry Council.
Cleaning often involves chlorine bleach, which has been used as a disinfectant for hundreds of years. But our bodies have been using bleach’s active component, hypochlorous acid, to help clean house for millennia. As part of our natural response to infection, certain types of immune cells produce hypochlorous acid to help kill invading microbes, including bacteria.
Researchers funded by the National Institutes of Health have made strides in understanding exactly how bleach kills bacteria—and how bacteria’s own defenses can protect against the cellular stress caused by bleach. The insights gained may lead to the development of new drugs to breach these microbial defenses, helping our bodies fight disease.
“When we started looking into how bleach actually kills bacteria, there was very little known about it,” says Ursula Jakob of the University of Michigan. In a series of experiments, her team showed that hypochlorous acid causes bacterial proteins to unfold and stick to one another, making them nonfunctional and leading to cell death.
By investigating how bacteria respond to stressful conditions, the Jakob lab has uncovered several ways that bacteria in our bodies—and on our kitchen counters—can survive attack by hypochlorous acid. One such survival mechanism uses a protein called Hsp33, which is a molecular chaperone that helps other proteins fold into and maintain their normal forms. Protection by Hsp33 lets bacteria refold their proteins once a stressful situation has passed, thereby allowing the cells to survive. The Jakob lab also has discovered several bacterial proteins that sense hypochlorous acid and, in response, activate genes that help the bacteria eliminate toxins produced by exposure to the noxious chemical.
Recently, the team discovered that a simple inorganic molecule called polyphosphate also serves as a molecular chaperone within bacterial cells. Polyphosphate, which likely existed before life arose on Earth and is produced by almost all organisms, from bacteria to humans, may be one of the oldest molecular chaperones in existence. Bacteria lacking polyphosphate are very sensitive to the cellular stress caused by bleach and are less likely to cause infection.
Together, these results provide insights into how modern-day bacteria defend against immune attack and how early organisms survived environmental challenges. The studies also point to potential targets for antimicrobial drug development. “Many of these protective mechanisms that bacteria use in response to bleach are specific to bacteria,” said Jakob, potentially making it possible to target these defenses without harming human cells. She and her team hope to find drugs to exploit this specificity and disarm bacterial defenses against bleach, allowing our immune systems to finish cleaning house.
The research reported in this article was funded in part under NIH grant R01 GM065318.
Source: NIH, National Institute of General Medical Sciences (NIGMS)