Small but mighty

Tens of thousands of previously overlooked tiny proteins are now being hailed as instrumental in advancing scientific understanding of how the microorganisms that dwell in and on our bodies affect our health, researchers have found.

What’s more, if their shapes and functions can be recreated in the lab, the knowledge could lead to new drug discovery, they said.

There’s mounting evidence that many aspects of our health are closely intertwined with the composition and hardiness of these microscopic hitchhikers, collectively known as the human microbiome.

The proteins, which belong to more than 4,000 new biological families, are predicted to be involved in the warfare waged among different bacterial strains as they vie for primacy in coveted biological niches.

They are so small — fewer than 50 amino acids in length — they likely fold into unique shapes that represent previously unidentified biological building blocks. A paper describing the research was published Aug. 8 in Cell.

“It’s critically important to understand the interface between human cells and the microbiome,” said senior author, Ami Bhatt, MD, PhD, assistant professor of medicine and of genetics. “How do they communicate? How do strains of bacteria protect themselves from other strains? These functions are likely to be found in very small proteins, which may be more likely than larger proteins to be secreted outside the cell.”

But the proteins’ miniscule size makes them difficult to identify and study. “We’ve been more likely to make an error than to guess correctly when trying to predict which bacterial DNA sequences contain these very small genes,” Bhatt said. “So until now, we’ve systematically ignored their existence. It’s been a clear blind spot.”