Cracking cryptic clues to the plague

Scientists in the US are modelling the behaviour of the bacteria responsible for bubonic plague to find alternative ways to target the disease. Using a novel approach called CryptFind, Eivind Almaas and Ali Navid from the Lawrence Livermore National Laboratory, US, have found the genes that the bacteria, Yersinia pestis, call upon to survive.

Plague circulates mainly among animals, via fleas

Although the plague is widely considered to be a disease of the past - it has killed 200 million people throughout human history - it still affects thousands of people worldwide. Whilst it can usually be treated using antibiotics, several antibiotic resistant strains have recently been discovered, indicating that new treatments for the plague are needed.

But it is very difficult to study plague behaviour experimentally because of fears over public safety and the need for high-security laboratory conditions (Yersinia pestis, the bacterial cause of the disease, is classed as a potential bioterrorism pathogen by US authorities). Therefore, theoretical models, such as those developed by Almaas and Navid, are used in place of clinical studies.

"By identifying candidate cryptic genes, it is possible to target not only the primary pathway to a compound, but also eliminate dormant alternate pathways."

The US researchers used CryptFind to identify Y. pestis' cryptic genes. These genes are not normally required for cell function, but can ensure cell survival under extreme conditions. Almaas explains that it is Y. pestis' ability to initiate cryptic genes that enables it to survive in hospital environments, and complicates the development of drugs for the plague. 'By identifying candidate cryptic genes,' he says, 'it is possible to target not only the primary pathway to a compound [essential for Y. pestis survival], but also eliminate dormant alternate pathways.'

Bernard Palsson, an expert in mathematical genome modelling from the University of California, San Diego, US, says that 'it is wonderful to see more reconstructions of human pathogens appearing. Hopefully, such reconstructions will open up new dimensions in the fight against infectious disease.'

Almaas is now in the process of modelling other Yersinia variants, including Yersinia pseudotuberculosis, a precursor to Y. pestis which causes tuberculosis-like symptoms in humans.

Hilary Burch

http://www.rsc.org/Publishing/Journals/cb/Volume/2009/3/cracking_cryptic_clues_to_the_plague.asp