Biolog said last week that it has been awarded a two-year, $1 million Phase II Small Business Technology Transfer research grant from the National Institute of General Medical Sciences to enable its Phenotypic Microarray technology to phenotype different strains of Mycobacteria.
The project is noteworthy because certain strains of Mycobacteria, such as M. tuberculosis, which the project will eventually study, have become resistant to most antibiotics and as a result have become lethal.
Biolog said that the principal goal of the STTR project is to adapt the PM technology for so-called “fastidious” bacterial groups, which require special conditions for culture and testing.
“The big reason we wanted to do it this way was to work on Mycobacterium tuberculosis,” Biolog CEO Barry Bochner told CBA News sister publication Biotech Transfer Week last week (see BTW , 10/15/07). “There is a lot of interest in Mycobacterium, and at Biolog we can work on some of the so-called fast-growing Mycobacterium species.”
The Phenotype Microarray technology tests a cell line against thousands of conditions or drugs in a highly multiplexed fashion. It could be considered a form of high-content screening that can also be performed in a high-throughput format.
Biolog’s collaborator on the project is Lacy Daniels, a professor of pharmaceutical sciences at Texas A&M Health Science Center’s Irma Lerma Rangel School of Pharmacy.
Daniels’ lab will work to develop methods for using the PM technology to specifically study the metabolism and physiology of Mycobacterium, Bochner said.
Daniels “has worked much of his career with Mycobacterium, and he has access to biosafety facilities that we wouldn’t have access to,” Bochner added.
Daniels told CBA News this week that he plans to begin the project with the
rapid-growing Mycobacterium that he currently works with, M. smegmatis, in order to develop the PM technology for this microorganism, and then move on to Mycobacteria strains that are more difficult to work with, such as M. bovis BCG.
Daniels said that M. bovis BCG is safe to work with and grows slowly, which makes it an easy microorganism to which to adapt the PM technology. He also said that while he works with non-pathogenic Mycobacterium strains in the lab, his primary area of interest is in M. tuberculosis.
“After we figure out the techniques using M. bovis BCG, than we will have access to a specialized biosafety facility that is more appropriate for working with M. tuberculosis,” said Daniels.
He said his lab will start within a few weeks with M. smegmatis, move on to M. bovis sometime during the grant’s first year, and then start working with M. tuberculosis during the second year.
“In my lab, we have an interest in examining phenotypic responses of the bacteria to mutations,” Daniels said. He added that he and his team are most interested in electron-transfer reactions in Mycobacterium, particularly those reactions that may affect drug resistance.
“After we figure out the techniques using M. bovis BCG, than we will have access to a specialized biosafety facility that is more appropriate for working with M. tuberculosis.”
Unfortunately, analyzing such reactions in Mycobacterium can be difficult because their genomes contain 3,000 to 4,000 genes, he said.
“If you make a mutation in one of the genes, one way of determining its function is to try to grow the mutant bacteria on a phenotypic array, and ask if it grows as well under all of these conditions as did the original wild type,” said Daniels.
Biolog’s PM technology, while used in a lot of different bacteria, has never been developed for use with Mycobacteria, he said.
According to Daniels, the Biolog system has been used principally with more commonly studied bacteria such as E. coli and bacteria that are easier to work with.
“So my end of the project is examining a pretty wide range of different Mycobacterium for, in essence, how well the Biolog PM system will identify these different mutant strains of bacteria,” Daniels said. “Then we plan to test some of the mutants that we have generated and continue to generate in the PM system.”
Daniels said his team had considered trying to develop their own method for phenotyping strains of Mycobacterium, but concluded that it would be too costly and time-consuming.
“Over the last four or five years, I have corresponded with Bochner a number of times, and we decided that the need was out there in the Mycobacterium field because a number of people who study Mycobacterium contacted him to see if Biolog’s system would work with Mycobacterium, and he always had to say no.”
Academic scientists together with the relatively few companies that are interested in Mycobacterium will likely be the primary customers for this PM application, Daniels said. The market is rather small in the US, said Daniels.
The World Health Organization estimates that approximately 33 percent of the world’s population is infected with M. tuberculosis, which kills about 12 percent of its hosts.