New strategies to fight the most dangerous infectious disease

Aug 31 2005

It has been identified by the World Health Organization as the most dangerous infectious disease, causing more deaths -- more than 2 million a year -- than any other single infection. Approximately one-third of the world's population is already infected.

"It" is Mycobacterium tuberculosis.

A Kansas State University chemistry professor is seeking to stem the tide in the war against TB. According to the WHO, no new antituberculosis drugs have been marketed during the last 30 years. As such, new strategies are needed to lead to the successful development of antituberculosis therapies.

K-State's Stefan H. Bossmann is researching a new strategy for treatment of the deadly infectious disease using ruthenium-polypyridyl-complexes as antimycobacterial drugs.

Bossmann's research explores unique physical and chemical properties of channel proteins called porins, isolated from Mycobacterium smegmatis and Mycobacterium tuberculosis. He is attempting to understand the working principles of porin channels in natural and artificial environments and he hopes to eventually develop supramolecular model systems to serve as physical models for the biological function of the porin systems.

"We have more and more resistant strains developing in Asia and Russia. We're also getting a large number of patients infected with TB immigrating to the United States," Bossmann said.

According to Bossmann, not many antibiotics actually work in treating TB because the disease has been steadily developing resistance to them. This makes new strategies for the delivery of drugs urgently needed, he said.

"It will become extremely difficult to treat cases of TB, in say 10 to 20 years down the road, because new treatment possibilities have not been developed," he said.

A "cocktail" consisting of a variety of drugs must be used to treat TB patients and they must be treated for several months, Bossmann said, but the problem with the conventional treatment is that microbacteria in TB grows slowly, helping it to evade the drugs.

"You might think this is a disadvantage, but it is not," Bossmann said. "The microbacteria has the talent to evade all of those medicines."

Mycobacterium TB has just a few pores in its outer walls which regulate basically all of its metabolics, Bossmann said. When the mycobacteria senses something dangerous like antibiotics, it simply closes the channel.

Bossmann's research is targeting the channels.

"It is the only way for the cells to have an exchange with the outside world as far as we know: to block them and put complexes in which bond irreversibly within those channels, depriving the channels of any possibility to take nutrients in or to discharge waste from its metabolism," he said. "This approach can permanently deactivate TB so that the human immune system can deal with it."