Protection for newborns: new treatment aims to prevent meningitis without antibiotics

Newborn meningitis is one of the most dangerous childhood infections. It is often life-threatening and can cause serious and lasting damage, including developmental problems, in the children who survive. Although meningitis is thankfully rare in newborns, it is more common in premature babies, affecting one in every 500 such infants in industrialised economies and likely more in developing countries.

One of the leading pathogens responsible for these meningitis cases is the K1 form of the E. coli bacterium. Now, researchers from the Biozentrum, University of Basel, and ETH Zurich have developed an approach in mice studies that seeks to prevent transmission to newborns.

Transmission during birth

In healthy people, E. coli K1 is often part of the intestinal flora. As a silent cohabitant, the bacterium causes no problems, as it is kept in check by other bacteria and the immune system.

However, pregnant women carrying the pathogen can transmit it to the child during birth. In premature babies whose immune systems are still weak, the pathogen can enter the bloodstream and migrate to the brain, where it causes severe inflammation.

First weaken the pathogen, then fight it

Researchers led by Professor Médéric Diard at the Biozentrum, University of Basel, and Professor Emma Slack at ETH Zurich want to stop transmission from happening in the first place. Their idea is to eliminate the pathogen in the intestine of pregnant women.

A year ago, the teams had already jointly developed a combination therapy for eradicating other pathogens in the intestine. They used two components: an oral vaccination that weakens the pathogenic bacterium, followed by a dose of harmless microbes that outcompete the weakened pathogen.

So tough that three components are needed

However, the K1 form of E. coli is a formidable opponent: unlike other E. coli bacteria, it is protected by a thick outer layer. This prevents the antibodies generated by the vaccination from attacking the bacterium. Slack and Diard therefore extended their previous two-pronged approach with a third component known as bacteriophages (or simply phages). These are viruses that specifically infect and kill bacteria.

The phages attack the bacteria by docking to the protective layer, and the bacteria seek to prevent this by rapidly disposing their layer. “This is essentially a resistance mechanism,” says Slack. “We use this mechanism to our advantage: the antibodies are effective against K1 bacteria without their protective coating.”

The project involved searching for effective phages. “We found the phages used in this study in waste water samples from a treatment plant of the Basel conurbation”, says Diard. “From such a sample, we successfully isolated several phages that are particularly effective at killing the bacterium E. coli K1.”

Most young animals protected

In experiments with pregnant mice infected with pathogenic E. coli K1, the researchers were able to demonstrate the effectiveness of their triple-pronged treatment combining phages, vaccination and harmless probiotic bacteria.

The treatment significantly reduced the level of E. coli K1 in the mothers’ intestines, such that the pathogen was only transmitted to 23 percent of the young animals. The remaining offspring were protected. In contrast, E. coli K1 was transmitted to 83 percent of young animals at birth when the mothers were not treated.

Works even when antibiotics fail

The researchers are now keen to continue with their approach in order to develop a treatment for humans. “In a world in which effective antibiotics are becoming increasingly scarce, we need new therapeutic approaches,” says Slack. “Bacteria such as E. coli K1 are difficult to tackle. Our approach is potentially the only one that can be used to fight this pathogen and others without antibiotics.”