Scientists are fusing sequencing, chemistry and imaging techniques to probe interactions between pathogens and their host cells.

Tuberculosis has been a scourge of humanity for millennia: the oldest known cases are in a pair of 9,000-year-old skeletons. Despite modern therapies, the disease affects about ten million people a year. It’s challenging both to treat, and to study in the laboratory.

Part of the difficulty is that the bacterium that causes it, Mycobacterium tuberculosis, holes up inside the very immune cells that the body deploys to fight it. Any treatments must therefore cross the human cell membrane before even attempting to attack the bacterium — a tricky manoeuvre. Similarly, researchers studying host–pathogen interactions must find ways to study the bacterium in cultured cells or in animals to capture the true complexity of the infection.

And it’s not just M. tuberculosis. Many other intracellular pathogens, including Salmonella typhimurium, Chlamydia trachomatis and Listeria monocytogenes, are best investigated in tandem with their host cells. “We basically pay as much attention to the pathogen as we do to the host,” says David Russell, an infection biologist at Cornell University in Ithaca, New York. “I really think you can’t interpret one without the other.”

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