February 04, 2014

Mycobacteria meeting focuses on TB

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Mycobacterium tuberculosis – which has been called “the perfect pathogen” – was the focus for nearly 100 researchers at the 5th biennial Southeastern Mycobacteria Meeting, held at UAB Jan. 24-26, 2014.

This bacterial pathogen causes a world-wide scourge of disease tuberculosis, especially in lesser developed countries.

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“It is estimated that nearly one-third of the people in the world are infected with Mtb (M. tuberculosis), said Michael Niederweis, Ph.D., a professor in the School of Medicine’s Department of Microbiology. Most of the infections are latent, persisting for years without disease, but “one to 1.5 million people die each year with TB, and there are 8 million recorded TB cases a year.”

The infection starts by inhaling a drop with just one to three bacteria. Mtb then subverts the immune system, preventing attack and destruction of the infectious invaders. Mtb attracts macrophage immune cells and other immune cells, and then multiplies inside them, eventually forming granulomas in the lung. The bacteria later can force the immune cells to destroy themselves, releasing the bacteria so they can be coughed out of the lungs on droplets of sputum or blood to infect other victims.

With the widespread antibiotic resistance of Mtb, it is vital to study how Mtb stymies the immune system at the cellular and molecular level, because those mechanisms can then become targets for possible new drugs.

The Southeastern Meeting particularly focused on young investigators, Niederweis said.

“The meetings have proven to be a wild success, particularly for the grad students and post-docs,” he said. “They have the same problems. Mtb is a much more difficult bacteria than all others. It’s difficult to grow, it clumps. It’s good to exchange your experiences; it’s good to know you are not alone.”

Miriam Braunstein, a professor at the University of North Carolina at Chapel Hill and meeting co-organizer, urged the young researchers to interact.

“My personal goal is to have all of you leave having met five people you can interact with later,” she said before the first session. In the question periods after each of the 17 talks, Niederweis threw a custom-made meeting T-shirt, with the slogan “Evading immunity … like forever”, to each first grad student who asked a question.

Some highlights of the meeting include:
  • Advanced biochemical and molecular understanding of various Mtb processes that may serve as targets for potential therapies. For example, Sylvie Garneau-Tsodikova, Ph.D., of the University of Kentucky revealed the function and molecular structure of a potent inactivator of aminoglycoside antibiotics, and she has begun the search for inhibitors of this Mtb enzyme. Daniel Kalman, Ph.D., of Emory University showed that Mtb co-opts a host (human) tyrosine kinase to help the bacteria enter into and survive inside of macrophage immune cells, and he said the cancer drug Gleevec – which acts against that same kinase – may help treat TB.
  •  Lalita Ramakrishnan, MBBS, Ph.D., the University of Washington, and Rebecca Beerman, Ph.D., Duke University, showed videos of macrophages hunting down and ingesting M. marinum bacteria in an animal model for TB, the transparent zebrafish. Beerman coupled the calcium signaling of macrophages with a green fluorescent dye, so the living cells flashed as they moved. If the cells ingested E. coli bacteria, they continued to flash but the flashing was turned off after ingesting M. marinum.
  •  UAB post-doc Jim Sun, Ph.D. described a novel and unusual Mtb protein toxic called CpnT. The toxin – a cleaved portion of a larger protein – is required for Mtb to survive in macrophages, and when the protein is induced, it causes necrotic cell death in human cells or other bacteria. Necrosis induced by Mtb allows the pathogen to exit macrophages and spread the virulent infection.
UAB hosted the first biennial Southeastern Mycobacteria Meeting eight years ago, followed by Chapel Hill, the University of Georgia and Emory. In introductory remarks at this year’s fifth meeting, Michael Saag, M.D., director of UAB’s Center for AIDS Research, said one hallmark of UAB through the years is how well its researchers worked together, sharing ideas. The Mycobacteria meetings, he said, are meant to feel the same spirit.

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“That’s why I’m so excited about this meeting. It’s a time to share ideas, work together. It’s almost impossible these days to have a single lab do research alone.”

The regional meeting was funded with the help of the Center for AIDS Research and the UAB Department of Microbiology. The money was well spent, says Saag.

“The meeting has huge value,” he said. “People talk science in the halls, and new collaborations are formed that spark new funding. That’s the new world of science.”

Contributed by Jeff Hansen for the UAB School of Medicine