How crafty E. coli can make IBD worse

More than one million Americans suffer from IBD (inflammatory bowel diseases), which includes a broad range of gastrointestinal tract problems such as Crohn's disease and ulcerative colitis. (Credit: iStockphoto)

Some strains of E. coli that normally live in our intestines are important for a healthy digestive tract. But, for people with inflammatory bowel diseases (IBD), these innocuous strains can proliferate during a flare-up and further contribute to disease and discomfort.

Now, researchers have defined a fundamental mechanism through which Escherichia coli thrive.

Opportunistic E. coli

More than one million Americans suffer from IBD, which includes a broad range of gastrointestinal tract problems such as Crohn’s disease and ulcerative colitis, the Centers for Disease Control reports.

“Several types of inflammatory bowel disease are characterized by expansion of the opportunistic E. coli in the gut,” says Matam Vijay-Kumar, assistant professor of nutritional sciences and medicine at Penn State.

“However, the mechanisms by which E. coli can thwart the hostile host innate immune system are poorly understood. Identifying these mechanisms will help to reduce the E. coli burden in the inflamed gut and prevent chronic extra-intestinal diseases.”

Fighting bacteria

For the new study, published in Nature Communications, researchers studied the interactions between enterobactin, myeloperoxidase, and lipocalin 2 and how they regulate E. coli in the intestine.

Enterobactin (Ent) is an iron-loving chemical secreted by E. coli that takes iron from host proteins in the body and aids the proliferation of E. coli. Myeloperoxidase (MPO) is an antibacterial protein that white blood cells produce to fight bacteria. However, Ent inhibits MPO from doing its job.

Lipocalin 2 (Lcn2) is another protein, also produced by white blood cells, that gathers up Ent—so that bacteria fail to obtain a sufficient amount of iron for their survival. The researchers found that Lcn2 can counter the effects of Ent on MPO.

“These bacteria can be harmful under special circumstances, such as IBD,” Vijay-Kumar says. “Most E. coli express enterobactin, a siderophore, and to avoid its recognition by the host lipocalin 2, they have the flexibility to express stealth siderophores. Strictly speaking, chelation of iron in the gut by enterobactin and inhibition of host MPO at the same time is positive for E. coli and negative for the host.”

Defense mechanism

The study defines a new defense mechanism used by E. coli residing in a human or animal host—the inhibition of MPO by Ent.

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“We have to find a way to identify the drugs which can inhibit or degrade secreted enterobactin,” Vijay-Kumar says.

“Alternatively, since MPO is known to be pro-inflammatory not only in IBD but also in other inflammatory diseases, it may be possible to develop enterobactin-based drugs to alleviate inflammatory pathways.”

Other researchers from Penn State, and from the University of Michigan, University of Copenhagen, and University of Toledo, collaborated on the research.

The National Institutes of Health supported the work.

Source: Penn State