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Tuberculosis infects a third of the world’s population, but less than 10 percent of those people actually get sick — a characteristic that has long puzzled researchers.

Seattle BioMed, a nonprofit that focuses on infectious-disease research, received a $16.6 million grant Thursday from the National Institutes of Health (NIH) to study how tuberculosis goes from latent infection to disease. Eventually, researchers hope to predict which carriers will become ill.

Public Health Seattle — King County says there are fewer than 150 active cases per year in the county, and fatalities are rare because of aggressive public-health measures.

Worldwide, though, tuberculosis is the second- largest killer from a single infectious agent after HIV/AIDS. In 2011, 8.7 million people become ill and 1.4 million died from the disease, the vast majority in developing countries, according to the World Health Organization.

Tuberculosis is especially problematic in countries with fewer health-care resources because it’s hard to diagnose, and the standard treatment of four drugs over six months requires strict adherence.

The research Seattle BioMed is undertaking — to be funded for five years by the NIH’s National Institute of Allergy and Infectious Diseases — takes a step back to answer basic questions about how the bacteria interacts with the body to cause disease. There are two parts to the project, one focusing on humans and one on the bacteria.

The first builds on work from the lab of Alan Aderem, co-principal investigator for the grant and president of Seattle BioMed. Over two years, his lab regularly collected blood samples from thousands of teenagers in South Africa who were infected with tuberculosis but were not sick. Some of them did eventually become ill.

Funded by the Gates Foundation, there’s been ongoing research with the blood samples to identify how gene expression differs in latent and active cases. The NIH grant will fund experiments using mice and human cells.

David Sherman, a full professor at Seattle BioMed, is the other co-principal investigator. He will lead a second part of the research that focuses on the bacteria. His lab has mapped out the bacteria’s gene-regulation networks, and his research team will put mutant bacteria in mice to study which gene regulators affect tuberculosis’ progression.

“I want to highlight the innovative nature of this project,” said Sherman, “We’re using system-biology tools and we’re really doing it in a cutting-edge kind of way. Our goal is to model the whole infectious process.”

Less than 20 percent of tuberculosis funding in 2011 went to basic-science research like this, according to a report by Treatment Action Group, a think tank for AIDS and diseases like TB that are often found in AIDS patients.

The majority goes toward discovering new drugs or diagnostic tools, but basic research into the bacteria can inform better treatment as well.

“While it’s not specifically the explicit goal of this program, we are focused, poised, eager to grab every insight for drug discovery,” said Sherman, whose lab also looks for new drugs.

Compared with other common infectious diseases, tuberculosis receives relatively little money. The NIH, the single largest funding source for medical research, spends roughly 15 times more on research into AIDS/HIV than tuberculosis. Much still remains unknown about the bacteria, which infects so many people across the world.

”Tuberculosis is such a remarkably well-adapted pathogen,” said Sherman. “That’s why so many people succumb.”

Sarah Zhang: 206-464-2195 or On twitter @sarahzhang