Arsenic Resistance Mechanisms

Arsenic is one of the most important environmental global toxicants that cause acute and chronic adverse health effects, including cancer. In many countries exposure to arsenic is a daily occurrence because of its environmental pervasiveness and millions of people around the world have been, and are, exposed to arsenic through geologically contaminated drinking water. Indeed, the incidence of exposure and consequent disease are at alarming proportions on the Indian subcontinent, where as many as 330 million people may be at risk. In an attempt to provide clean drinking water, millions of tube wells have been sunk on the Indian subcontinent, but unfortunately it was not realized that this water would become contaminated by arsenic. Arsenic poisoning is considered to be the greatest single-cause of ill-health in the world today.

The ubiquity of arsenic in the environment has led to the evolution of similar defence mechanisms in organism ranging from bacteria to man. If we are to understand the mechanisms and better address the problems associated with arsenic toxicity then it will be necessary to elucidate the mechanisms controlling cellular arsenic levels. We aim to elucidate aspects of a regulatory system that controls arsenic levels in bacteria. Both bacteria and mammalian cells utilise proteins that span cellular membranes, where they act as bilge pumps, reducing the cellular concentration to sub-toxic levels. We have found that bacteria produce a so called metallochaperone that sequesters arsenic within the bacterium for delivery to the pump, presumably enhancing the ability of the bacterium to detoxify cellular arsenic. Our aim is to better understand the role of this metallochaperone in arsenic detoxification. A spin-off of our studies is that it may identify proteins that can be used as molecular probes for detecting arsenic in the field and in decomtaminating water at the increasingly stringent levels that are being applied around the world, and which are currently difficult to achieve and monitor with our current technology.