Bacteria stole genes from gut microbes to cause deadly meningitis outbreak

A severe outbreak of invasive meningococcal disease, which can cause meningitis and sepsis, in Kent in the UK earlier this year was driven by a bacterial strain that took genes from harmless microbes. This helped the resulting bacteria evade the immune system and obtain iron from blood, boosting their growth.

“What was really unusual about the outbreak is quite how explosive it was,” says Emma Wall at Queen Mary University of London, who wasn’t involved in the discovery. “[The bacterium] clearly gained a set of genetic changes that made it better at hiding from the immune system and better at harvesting nutrients. That made it a really super powerful bug.”

In March, 21 people – mostly university or high school students – are known to have become infected with a strain of Neisseria meningitidis group B at a nightclub in Canterbury, Kent. N. meningitidis usually spreads via close and prolonged contact with saliva from an infected person via things like kissing and sharing drinks or vapes.

N. meningitidis lives harmlessly in the nose and throat of between 5 and 10 per cent of people without causing any health problems, but genetic changes can allow it to become more invasive and enter the bloodstream, leading to invasive meningococcal disease (IMD). This can result in sepsis, a life-threatening immune reaction to bacteria, or meningitis, where bacteria infect the thin lining surrounding the brain and spinal cord, causing inflammation.

All the IMD infections in Kent occurred within about a week. Those infected were treated in hospital, with nine requiring intensive care. “The incredibly rapid nature of the outbreak was unprecedented [for the UK],” says Wall. “Usually these [outbreaks] roll over two or three weeks and there’s one or two cases that end up in hospital.”

To understand this, Martin Maiden at the University of Oxford and his colleagues sequenced the entire genome of live N. meningitidis in blood samples taken from six of those infected, including the two people who died.

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These bacterial genomes were almost identical, suggesting the outbreak started from one person. Next, the team compared one of these genomes with 48,000 others from Neisseria strains collected during prior outbreaks or from people without known health problems.

This revealed that the Kent strain had acquired several genes from a harmless strain of N. meningitidis and another bacterium called Neisseria cinerea that lives harmlessly in up to 28 per cent of adults. Bacteria constantly exchange genetic material via a process called horizontal transfer, which can involve them forming tiny tunnels between each other, through which they transfer copies of genes.

Some of the genes acquired by the Kent strain enhanced its uptake of iron from blood, which it needs to survive and replicate. Others reduced the amount of sugar that was coating a tail-like structure, called the pilus, on the bacterium. This enabled bacteria to clump together and evade destruction by immune cells, such as neutrophils. “Neutrophils will try and come and eat an individual [bacterium], but they can’t eat a clump, it’s too big,” says Wall.

“There was this catalogue of changes that made this organism really transmissible, but also really invasive,” says Maiden. This meant that several people became very ill and were then less able to transmit the infection to the public. “If you’re ill, you’re not going to be going around transmitting organisms, so the outbreak ended very quickly,” says Maiden.

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It is unclear exactly when these genetic changes occurred in the person believed to have initiated the outbreak, but they probably happened gradually, until there was the right combination of genetics and social mixing, says Maiden.

Such insights could support the development of better vaccines against N. meningitidis if we can target the features that make the bacterium particularly invasive, says Wall. But they won’t help us predict the next highly invasive strain. “[These bacteria are] inherently highly unpredictable,” says Maiden.

Following the Kent outbreak, the UK government launched a vaccination programme for young people starting university or further education in September or October this year. Symptoms of IMD include fever, headache, a stiff neck, joint and muscle pain, and a rash that doesn’t fade when pressed with a glass.

Source: Severe meningitis outbreak caused by bacteria that took genes from microbiome