Researchers have found out how E. coli knows where and when to begin colonizing the colon ahead of making people sick.

By recognizing the low-oxygen environment of the large intestine, the foodborne pathogen gives itself the best chance to establish a robust infection.

A pair of University of Virginia School of Medicine scientists revealed how E. coli finds the most oxygen-free crevices of the colon to cause the worst infection possible. They hope the discovery could let doctors prevent infection by allowing E. coli to pass harmlessly through the body, according to the study published in the Proceedings of the National Academy of Sciences (PNAS) journal.

E. coli naturally lives in the colons of humans, and most strains do no harm. But some types can cause cramps, diarrhea, vomiting, even kidney failure and death, with children particularly at risk.

E. coli waits for right oxygen levels
Bacterial pathogens typically colonize a specific tissue in the host and as part of infection strategies they time deployment of proteins and toxins to these specific niches in the human host.

“This allows the pathogens to save energy and avoid detection by our immune systems and ultimately cause disease. By knowing how bacterial pathogens sense where they are in the body, we may one day be able to prevent E. coli, as well as other pathogens, from knowing where it is inside a human host and allow it to pass through the body without causing an infection,” said researcher Melissa Kendall, of UVA’s Department of Microbiology, Immunology and Cancer Biology.

Kendall and graduate student Elizabeth M. Melson outlined a process E. coli uses to detect low oxygen levels in the large intestine and then produce proteins that allow it to attach to host cells and establish infection.

Oxygen diffuses from the intestinal tissue into the gut, and there are higher levels in the small intestine than the large. E. coli waits until it has reached the-low oxygen large intestine before striking.

Blocking oxygen sensing
E. coli has a small form of RNA that activates particular genes when oxygen levels are low enough, according to the study. At this point the infection gets established and due to this natural sensing process, the bacteria are able to establish infection and begin to manufacture Shiga toxins.

The small RNA DicF is a key factor in the ability of enterohemorrhagic E. coli O157:H7 (EHEC) to sense the low oxygen environment of the colon to enhance virulence, through PchA. DicF disrupts intramolecular interactions that normally inhibit PchA expression.

Commensal E. coli encode one dicF gene but EHEC acquired three additional dicF copies during its evolution. This suggests oxygen sensing and virulence regulation through DicF provides EHEC with a strategy to amplify virulence within its host colonization niche.

In oxygen-limited conditions, DicF enhances global expression of the EHEC type three secretion system, which is a key virulence factor needed for host colonization, through the transcriptional activator PchA.

“If scientists can figure how to block oxygen sensing, we may be able to prevent E. coli from making proteins that allow it to stick to our guts. This may be an effective strategy to limit infection, and because we are not targeting growth or survival, E. coli may not develop drug resistance – it just doesn’t know where it is,” said Kendall.

Researchers believe other bacterial pathogens, such as Shigella and Salmonella, likely employ a similar control mechanism, though more work needs to be done to back up this theory.

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