Why one vaccine cannot protect against all E. coli infections

The bacterium E. coli is the most common cause of urinary tract infections and bloodstream infections. But in the search for vaccines, researchers have discovered that the bacteria are more resilient than they had thought.

Most people have E. coli as part of their gut microbiota. As long as it stays in the gut, it generally doesn't cause trouble. But if it ends up in other parts of the body, it can lead to infection, such as urinary tract infections and bloodstream infections. This can be particularly serious for older people and those with cancer.

Becoming more and more antibiotic-resistant

Many people are given antibiotics to cure an infection. However, the frequent use of antibiotics has led to a number of variants of E. coli becoming multi-resistant. This means that several types of antibiotics no longer work against them, which poses a major threat to public health.

A vaccine could reduce antibiotic resistance

Researchers therefore hope that it will be possible to develop vaccines against the bacterium.

"It could both reduce the use of antibiotics and be of great benefit to people with weakened immune systems, such as older people and cancer patients," explains Rebecca Gladstone. She is a researcher at the Department of Biostatistics at the Institute of Basic Medical Sciences at the University of Oslo.

One vaccine will not work against all infections

In a new study published in Nature Microbiology, she and her collaborators collected data from 18,000 patient samples in a number of countries around the world. They studied the details of the bacterium's genetic material through so-called genome sequencing.

E. coli, like bacteria in general are tough survivors and therefore have a protective capsule around them. Such capsules are made of different types of sugar layers that the bacteria hide behind to evade our immune system and to resist other environmental pressures.

And here the researchers encountered a new challenge in the study. They found that there was more variation in this protective system than they had assumed.

We discovered 90 different variants of such protective capsules on E. coli bacteria. Only a third of these were previously known."

Rebecca Gladstone, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo

Researchers will target vaccines at the most common variants causing infections

There are, however, in countries such as Norway, a handful of variants that account for half of the urinary tract infections and bloodstream infections. These in turn cause many of the infections where the bacterium is resistant, meaning that it withstands at least one type of antibiotic.

"The two most common capsules, K1 and K5, mimic human sugar-coated proteins residing on the surfaces of our cells. So these cannot be used directly in vaccines. For bacteria that have these two types of capsules, we therefore have to find other features of the bacterium for the vaccine to target," says Gladstone.

"In Norway, we can still achieve a lot if we develop vaccines that deal with just a few types of protective capsules. In low-income countries, the picture is more complicated," Gladstone says.

"There they have even greater variation in these protective capsules. In any case, this means we cannot develop just one vaccine that will work against all E. coli bacteria. We will most likely have to focus our efforts on the types that most often cause infections, and those that lead to the most severe infections."

Researchers must find new ways to kill the bacteria

In the future, we may risk having no treatment for infections if bacteria become resistant to all life-saving antibiotics.

"In addition to vaccines, we also need to work on developing rapid diagnostics. It will also be important to find methods of killing the bacteria without resorting to large amounts of broad-spectrum antibiotics," says Gladstone.

The study was carried out in collaboration with researchers from the Wellcome Sanger Institute and is partly funded by the Trond Mohn Research Foundation.