Multidrug-resistant tuberculosis challenges scientists

Elizabeth Polsdofer

While the battle of the future of America’s healthcare is being waged in the political sphere, the battle for several million lives is being waged by doctors and scientists all over the world as a strain of multidrug-resistant tuberculosis has emerged. This new strain is completely resistant to antibiotics and therefore is untreatable.

Ed Yu, a researcher at the U.S. Department of Energy’s Ames Laboratory and professor at Iowa State, is working on discovering the reason tuberculosis is now drug resistant.

“Nine million people are infected each year and also 2 million people will die because of that each year as well. In terms of infectious disease this is second to HIV,” Yu said. “We are just working on basic research in our lab. We try to understand the mechanism that interferes with the effectiveness of the drug.”

Normally, when an antibiotic enters the body, the tuberculosis bacteria would absorb the antibiotic. Like a rat eating rat poison, the bacteria would “eat” the antibiotic and would, consequently, die. The problem with the new strain of tuberculosis is that it now knows better and is able to spit out the rat poison — the antibiotics — when it knows what it has eaten.

“Bacteria have these things called pumps that exist that span the membrane and these pumps allow certain molecules to come in and they also allow certain molecules to go out,” said Guru Rao, the professor and chair of the Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology. “Over the last 30-35 years these bacteria have become resistant to various drugs that have been treated by antibiotics. The reason they have become resistant is possibly because these pumps have mutated.”

Rao and Yu said these mutations have occurred because of misuse of antibiotics. Whenever a patient receives antibiotics, their doctor tells them to continue taking the full course of antibiotics, even if the patient feels better after a day or two. The patient feels better because the antibiotics have killed off most of the bacteria, but the problem lies in the remaining bacteria. The surviving bacteria need to be killed off, if they are left alive, they will evolve and come back with a vengeance.

“We misuse antibiotics, that’s one thing. The way tuberculosis evolved into multi-drug resistance is during the treatment we didn’t treat the patient well enough,” Yu said. “Say they didn’t use enough dosage or during the treatment, it’s a long treatment that takes six months, for the first two months the patient feels better and then they don’t use the antibiotics anymore.”

“Drug resistance is a big thing,” Rao said. “I don’t know how long we’ll be able to give that pink medicine to our kids.”

How does one begin to combat a bacteria that is resistant to every antibiotic known to man? That’s where Yu comes in. The focus of Yu’s work is to help understand the pumps of the tuberculosis so scientists can create an antibiotic that the tuberculous bacteria cannot cough up.

“Shape matters in biology and bacteria have developed these sophisticated mechanisms for removing toxic materials from themselves,” Rao said. “Understanding how these molecules come together and looking at the 3-dimensional structure allows us now to design new molecules that will allow us to prevent the bacteria from becoming resistant.”

Rao said that the process to make antibiotics — the research Yu does — is groundbreaking.

“It’s a phenomenal piece of work. This is really important stuff. I think it’s a great credit to [Yu] and the institution that we have something like this happening here. [Yu] is remarkably understated about this whole thing,” Rao said. “This is phenomenal stuff; this gives me goosebumps.”