Mostly Harmless: Exploring how our bacterial friends become foes
Every surface, nook and cranny of the human body is inhabited by bacteria, with over 1000 different species calling our bodies home . Don’t panic! Most are totally harmless bacteria, known as commensals. Some are even beneficial to our health. Only a tiny proportion of bacterial species are pathogens, responsible for causing infectious diseases ranging from mild acne to life-threatening blood poisoning. Some bacteria fit neatly into one of these categories, commensal or pathogen. Lactobacillus casei for instance never causes disease, whilst infection with Borrelia burgdorferi almost always results in Lyme disease. However, many of the bacteria that we think of as pathogens are better described as “mostly harmless”. They normally live inside us without causing any symptoms, and only rarely cause disease. By studying the biological factors that tip the balance toward disease, the goal is to try and manage disease and prevent people from getting ill.
Neisseria meningitidis, the meningococcus, is a perfect example of a mostly harmless pathogen. As its scientific name suggests, the meningococcusis a leading cause of meningitis and blood poisoning, which is of course very harmful indeed. However, it’s far more commonly found living harmlessly in the nose or throat; recent surveys have found that the meningococcus may be living in up to 6% of teenagers at any given time , with absolutely no ill effects. Now consider that there are about 7 million 15-24 year olds in England , so as many as 420,000 could have meningococci living inside them, yet last year there were only 123 cases of disease in this age group . So the question is: what are the common factors that caused 123 people to get seriously ill, whilst thousands more were unharmed?
It turns out that there are many bacterial (and some human) factors involved. One factor that is virtually essential for meningitis is the possession of a capsule. You can think of it as a sort of bacterial invisibility cloak surrounding the outer surface of the bacterium, which meningococci use to hide from the body’s immune system. There are 12 variants of the meningococcal capsule, and some variants are better at hiding from the immune system than others. Five of these variants, imaginatively named A, B, C, W and Y, are so good at hiding from the immune system that, if they get into the bloodstream, they can proliferate unchecked, resulting in meningitis. Since the capsule plays such an important role in disease, learning about its biology is really helpful for biomedical research into the meningococcus.
One breakthrough has been the subversion of the deadly capsule variants to develop meningitis vaccines. The MenACWY vaccine trains the immune system to recognise bacteria that possess, you guessed it, capsules A, C, W or Y. This means that if you get infected in the future by meningitis A, C, W or Y, the bacteria can no longer hide behind their capsule, and are cleared by the immune system before they can cause disease. Meanwhile, friendly meningococci that don’t possess these deadly capsule variants are left undisturbed. Through our understanding of capsule biology, it has been possible to prevent thousands of cases of meningitis. This is a great achievement, but there is still much that we don’t yet know about capsules.
Firstly, how did meningococci acquire a capsule in the first place? My research suggests that the meningococcal capsule has a very complicated evolutionary history. I’ve shown that many non-pathogenic Neisseria species also possess their own capsule variants . This is interesting enough in itself, but notably, no isolates belonging to the five Neisseria species most closely related to the meningococcus possess capsules. It seems that the capsule may have been lost from a common ancestor of this group, and then much later, the meningococcus reacquired a capsule by swapping DNA with another encapsulated Neisseria species (I did say it was complicated!). This event gave the meningococcus the potential to become harmful, and provides an interesting insight into how novel pathogens might emerge. It further raises the question as to whether a new capsule variant could emerge in the future, with potential implications for public health.
Secondly, we don’t actually know why meningococci have capsules. Almost everything we know about the function of the meningococcal capsule concerns its role in disease, but we know little about what it might be doing when it lives harmlessly in the nose and throat. Exploring the capsule’s role in this more typical, harmless stage of the meningococcal lifecycle might help us understand more about the transition to disease.
The relationship of many pathogens like the meningococcus to their human hosts is much more nuanced than a simple dichotomy of good bacteria vs bad bacteria. By examining factors that make our bacterial friends become our foes, we can increase our understanding of bacterial pathology, epidemiology and vaccination strategies, which in turn bring benefits to public health.
Lloyd-Price J., Abu-Ali G. & Huttenhower, 2016. The healthy human microbiome. Genome Med 8(51)
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