February 22, 2023 - Podcast

Episode 347 — How bacteria survives the human body

David Giedroc, along with his team of researchers at Indiana University's College of Arts and Sciences, have discovered what they believe is a new key to understanding bacterial defense strategies during infections. Their recent publication describes the discovery and characterization of the transporter EgtU, which sets the stage for further exploration of these bacterial defense mechanisms.

Giedroc, distinguished professor and Lilly chemistry alumni professor, says the human immune system has dozens of ways to fight off invaders and when they recognize something foreign, one of the major reactions hosts can do is to send highly reactive oxygen-containing species to clear it. These attacks cripple essential bacterial processes which leads to cell death.

Their research shows that many bacteria, including those found in the human gut, appear to protect themselves using the dietary antioxidant called ergothioneine (ET). Luckily for bacteria, human tissues naturally have ET, so all they must do is find a way to take up ET from their environment. Giedroc's group, as well as another group working independently from Yale University, for the first time, have discovered how the bacteria do it. 

Giedroc’s group examined a specific bacterium where some strains of which can cause pneumonia in humans and found that it produces a protein that transports ET into the cell. They named this transporter EgtU and immediately began to explore its function. 

They found that EgtU has a very specific and crucial role. It is found on the outside of the bacterial cells, searching the surroundings for free ET. When it comes into contact with this dietary antioxidant, it captures it and ushers it into the bacterium’s interior. Once inside, ET can start its presumed job of protecting the cell from oxidative immune system attacks.

The researchers used a multidisciplinary approach to obtain a better understanding of EgtU, pairing cutting-edge mass spectrometry with state-of-the-art biological nuclear magnetic resonance spectroscopy.

One of the great things about IU is the ready availability of sophisticated instrumentation and professional staff to drive research projects forward, Giedroc says. Mass spectrometry showed unequivocally that functional EgtU is absolutely required to detect ET inside cells; in other words, these bacteria cannot make it. X-ray crystallography gave the researchers a molecular picture of the transporter, showing exactly how it binds to ET. Nuclear magnetic resonance spectroscopy showed that the transporter wants to bind to ET and nothing else. Together, these findings uncover part of the mystery of how bacteria can survive in the harsh environment of the human body. 

This discovery by Giedroc and his team, including IU students, provides essential information about how we fight bacterial infections.

Interestingly, the group found that both "good" and "bad" bacteria seem to be able to make this transporter. They found the transporter sequence in harmless bacteria, but also in bacteria associated with food poisoning, urinary tract infections, and staph infections.

All these bacteria cannot produce ET on their own, so they must steal it from their host. Humans have a limited amount of ET, meaning that the "good" and "bad" bacteria may well be in constant competition with the host for the body’s supply. Exactly what this implies for infections, the researchers aren't yet sure. But, Giedroc says this discovery foreshadows something big in the field.