A severe outbreak of invasive meningococcal disease, which can cause meningitis and sepsis, in Kent earlier this year was driven by a bacterial strain that took genes from harmless microbes. This helped the bacteria evade the immune system and obtain iron from blood, boosting their growth.
鈥淲hat was really unusual about the outbreak is quite how explosive it was,鈥� says at Queen Mary University of London, who wasn鈥檛 involved in the discovery. 鈥淸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.鈥�
In March, 21 people 鈥� mostly university or high school students 鈥� are known to have become infected with a strain of the bacteria Neisseria meningitidis group B at a nightclub in Canterbury, Kent in the UK. N. meningitidis usually spreads via close and prolonged contact with saliva from an infected person via things like kissing and sharing drinks or vapes.
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N. meningitidis lives harmlessly in the nose and throat of without health problems, but genetic changes can cause it to become more invasive and enter the bloodstream, leading to invasive meningococcal disease (IMD). This can cause sepsis, a life-threatening immune reaction to the bacteria, or meningitis, where bacteria infect the thin lining surrounding the brain and spinal cord, causing inflammation.
All the IMD cases in Kent occurred within about a week. They were treated in hospital, with nine requiring intensive care. 鈥淭he incredibly rapid nature of the outbreak was unprecedented [for the UK],鈥� says Wall. 鈥淯sually these [outbreaks] roll over two or three weeks and there鈥檚 one or two cases that end up in hospital.鈥�
To understand this, at the University of Oxford and his colleagues sequenced the entire genome of live N. meningitidis in blood samples taken from six of the cases, including the two people who died.
The bacterial genomes from the six cases 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 Neisseria meningitidis and another bacterium that lives harmlessly in , called Neisseria cinerea. Bacteria constantly carry out such genetic exchanges 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 bacteria. This enabled them to clump together and evade destruction by immune cells, such as neutrophils. 鈥淣eutrophils will try and come and eat an individual bacteria, but they can鈥檛 eat a clump; it鈥檚 too big,鈥� says Wall.
鈥淭here was this catalogue of changes that made this organism really transmissible, but also really invasive,鈥� says Maiden. This meant that several people became very ill and were then less able to transmit the infection to the public. 鈥淚f you鈥檙e ill, you鈥檙e not going to be going around transmitting organisms, so the outbreak ended very quickly,鈥� says Maiden.
It鈥檚 unclear when exactly these genetic changes occurred in the person who is thought 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 bacteria particularly invasive, says Wall. But they won鈥檛 help us predict the next highly invasive strain. 鈥淸These bacteria are] inherently highly unpredictable,鈥� says Maiden.
Following the Kent outbreak, the UK government launched a 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鈥檛 fade when pressed with glass.
bioRxiv
