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Microbes pepper our tissues with mysterious tiny proteins likely to affect health

The bacteria in our gut make tiny, previously unidentified proteins that could shed light on human health and advance drug development.

Like it or not, each of us is colonized by untold numbers of bacteria, viruses and other microbes. Collectively these creatures are known as the human microbiome, and there's a growing awareness that they play important roles in many aspects of human health from nutrition and digestion to premature birth. Exactly how they do so, however, is in many cases unclear.

Now geneticist Ami Bhatt, MD, PhD, and postdoctoral scholar Hila Sberro, PhD, have discovered that our tiny passengers are churning out even tinier proteins likely to make a big impact on neighboring bacteria and human cells. The proteins, which are fewer than 50 amino acids in length, have gone unnoticed in previous studies because their minuscule size has allowed them to slip through the nets cast by previous studies of the microbiome. They published their research today in Cell.

As I explain in our release:

The proteins belong to more than 4,000 new biological families predicted to be involved in, among other processes, the warfare waged among different bacterial strains as they vie for primacy in coveted biological niches, the cell-to-cell communication between microbes and their unwitting hosts, and the critical day-to-day housekeeping duties that keep the bacteria happy and healthy.

Because they are so small -- fewer than 50 amino acids in length -- it's likely the proteins fold into unique shapes that represent previously unidentified biological building blocks. If the shapes and functions of these proteins can be recreated in the lab, they could help researchers advance scientific understanding of how the microbiome affects human health and pave the way for new drug discovery.

Small proteins are especially difficult to identify because the current methods of pinpointing genes (which encode the instructions to make proteins) within a genome are particularly likely to fail when the target is exceptionally small. In fact, any potential small gene is more likely to be a false positive than a true hit.

But Sberro devised a way to compare potential positives across many different samples and bacterial species. Those that occur repeatedly are more likely than others to represent valid findings, she and Bhatt felt.

The approach worked, and Sberro identified tens of thousands of novel genes encoding tiny proteins. Many of these are likely to target neighboring cells for communication or defense, the researchers found. Unraveling their functions will help researchers learn how, for better or for worse, our minuscule microbes micromanage their hosts. It might also provide clues to the development of new antibiotics or other drugs.

As Bhatt explained: "It's critically important to understand the interface between human cells and the microbiome. How do they communicate? How do strains of bacteria protect themselves from other strains? [...] We anticipate this to be a valuable new area of biology for study."

Photo by Marcin Bajer

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