The human immune system has dozens of ways to fight off invaders. When they recognize something foreign, “one of the major things hosts can do is to deploy highly reactive oxygen-containing species to clear it,” noted Giedroc. These attacks cripple essential bacterial processes which leads to cell death.
The group’s publication 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 have to do is find a way to take up ET from their environment. Giedroc’s group, for the first time, has discovered how the bacteria do it.
The group examined the bacterium Streptococcus pneumoniae—some strains of which can cause pneumonia in humans – and found that it produces a protein whose job it is to transport ET into the cell. Another group at Yale University, working independently of Giedroc’s group, made the same observation in the gut pathogen Helicobacter pylori, publishing in Cell, speaking to the significance of the work. They fittingly named this transporter EgtU (ergothioneine uptake) and immediately began to explore its function.
As it turns out, EgtU has a very specific and very crucial role. It is found on the outside of the bacterium, 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 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 (NMR) spectroscopy.
“One of the great things about IU is the ready availability of sophisticated instrumentation and professional staff to drive research projects forward,” said Giedroc. 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 researchers a molecular picture of the transporter, showing exactly how it binds to ET. NMR spectroscopy showed that the transporter wants to bind to ET and nothing else. Together, these findings solve part of the mystery of how bacteria can survive in the harsh environment of the human body.
Giedroc’s research was supported by a grant from the National Institutes of Health.
Professor Steven Tait, Chair of the Chemistry Department, is optimistic about the findings. “This latest result by Professor Giedroc and his team, including IU students, provides essential information about how we fight bacterial infections,” he said. “This is an exciting discovery that exemplifies the high-impact research being done on our campus.”
Interestingly, the group found that both “good” and “bad” bacteria seem to be able to make this transporter. Using techniques in bioinformatics, the researchers compared the sequences of thousands of bacteria to that of Streptococcus pneumoniae. They found the transporter sequence in harmless bacteria, but also in bacteria associated with food poisoning, urinary tract infections, and staph infections.
All of these bacteria can’t produce ET on their own, so, like Streptococcus pneumoniae, 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 for the body’s supply. Exactly what this implies for infections, the researchers aren’t yet sure. But, Giedroc explained, “this discovery portends something big in the field.”
