Taking a strategic pause

Mycobacterium tuberculosis (Mtb) is a wily foe, adept at bobbing and weaving around the immune system and antibiotics alike, and sometimes lying dormant for years.

“It’s a very smart bacterium, with a lot of tricks,” says Shixin Liu, head of the Laboratory of Nanoscale Biophysics and Biochemistry.

Liu has pulled the curtain back on one such trick, working with Jeremy M. Rock and Corinne P. Greenberg Women & Science Professor Elizabeth Campbell, who heads the Laboratory of Molecular Pathogenesis. Together, they found that Mtb can control its gene expression by pausing transcription, or the process by which DNA is copied to RNA. Taking transcriptional “breathers” may give the bacterium a chance to adapt to changing conditions, such as a different environment or the presence of antibiotics.

Data

Number of people living with inactive TB in the U.S., according to CDC estimates.

Previously, bacteria weren’t thought to prominently use such strategic pausing to regulate their gene expression, which is common in more complex organisms. “The findings were so unexpected that I initially didn’t believe them,” says Rock, the Penrhyn E. Cook Associate Professor and head of the Laboratory of Host-Pathogen Biology.

Their startling discovery came via new technology: SEnd-seq, a high-resolution RNA sequencing tool developed by Liu and Xiangwu Ju, a senior research associate in the Liu lab, which the team used to analyze Mtb’s RNA transcripts at an unprecedented level of detail.

The researchers suspect that homing in on the pausing mechanism could provide a particularly fruitful avenue for identifying new drug targets against their cunning bacterial adversary.

“We can use this information to think about how we might inhibit its life cycle,” Liu says.