My holidays were great, thanks for asking. To start off the New Year I thought it was about time I wrote about the microbe I work on, Streptococcus pneumoniae. S. pneumoniae or the pneumococcus (pneumo to us in the lab) is widely considered to be one of the most successful pathogens on this planet. Wherever we look for it we find it and as of writing it is considered endemic in all human societies around the world. Alongside its huge spread in our population it is also responsible for some very costly diseases (in terms of both financial and human health).
It’s Not All Bad
Everything I have said about pneumo in the preamble above is true, but the pneumococcus is also responsible for, or contributed greatly to, some of the most important scientific discoveries of all time. The pneumococcus was independently isolated in 1880 by two researchers in the USA and France (two gentlemen named Sternberg and Pasteur – you may have heard of the last name). Although not working together, both scientists identified the bacteria as “roughly lancet shaped pairs of coccoid bacteria” – which turned out to be the first important discovery. The pneumococcus was the first bacteria species found to exist as a diploid, two organisms together (as can be seen above). As the bacteria divide new ‘doublets’ associate to form long chains that allow the bacteria to stay together and form a colony.
In 1884, it was used to develop a protocol called a Gram stain which is still used today as an indicator of what the bacterial surface looks like. This information is vital as it allows us to predict which antibiotics will work on the bacteria and which will not. By the early 1890’s, it was being used in immunology research and was involved in major work describing how the immune system worked. In 1912, the pneumococcus was identified as the first bacterial species to have developed a resistance to an antibiotic over time. This work was largely forgotten as antibiotics as we think of them today were not developed until after World War 2. The list goes on and on.
Arguably the most important discovery made with the aid of the pneumococcus was the discovery of DNA. Watson and Crick had their world-changing letter to Nature published in 1953 detailing the discovery of the structure of DNA but a full decade earlier an equally brilliant scientist Oswald T. Avery identified its purpose. Avery’s experiment relied on the fact the pneumo produces a structure called a capsule. You can think of it like an overcoat for the bacteria. This overcoat comes in a number of colours and styles but still all are able to act as an overcoat. Avery showed that he could take pneumo A, kill it, and mix it with pneumo B. Over time some pneumo B would express or ‘wear’ pneumo A’s overcoat. More importantly he showed this never happened in the presence of an enzyme that destroyed DNA, proving that it was the DNA transferring this information.
So It’s a Bit Bad
The spectrum of diseases capable of being caused by the pneumococcus is staggering and ranges from irritating ear aches to the very serious disease; necrotising fasciitis which has caused William Osler (famous medical textbook author), to refer to pneumo as “Captain of the Men of Death” by . The more common diseases are classified into two categories: invasive and non-invasive pneumococcal diseases.
Of the non-invasive diseases, the most important is Otitis media. Otitis media is more commonly known as a middle ear infection and can technically be caused by anything but the pneumococcus tops the list. You might be wondering how the bacteria, which we typically associate, you know, with pneumonia, can get into your ear. Currently we don’t actually ‘know’ but we have a pretty good idea. Children develop Otitis media more than any other age group; children stick their fingers in their noses and their ears. The other possibility is that the bacteria, after residing in your throat move up into the sinuses until they reach the middle ear. Otitis media, whilst it doesn’t kill very often is an enormous issue.
It’s been estimated that by the age of 5, the majority of children will have had 3 middle ear infections (~2 caused by pneumo) requiring treatment and several more cases that went undetected. Otitis media is also expensive as we have to buy antibiotics to treat it and sometimes things go wrong requiring a tympanostomy (a surgical procedure where the membrane of the eardrum is pierced to allow drainage of fluid). The government contribution to these treatments was estimated at $140 million in 2004 in Australia alone. As we administer so many antibiotics to treat Otitis media and pneumo is its leading cause, it has been proposed that the pneumo has more antibiotics prescribed for it that any other bacteria.
The remaining ‘common’ pneumococcal diseases are the invasive diseases; pneumonia, bacteraemia and meningitis. Pneumonia is most commonly associated with the pneumococcus but is often only caused as a ‘secondary infection’. The pneumococcus lives in your throat and will normally do so without you feeling sick. It’s so good at doing this that if you sampled everyone you know that is currently healthy all of them would still have the pneumococcus on their throats. But if you get sick, say the common cold, the pneumococcus can descend into the lung. Once in the lung the bacteria releases a toxin that breaks up cells and starts to grow in a place called the alveoli. This is the place in the lung where oxygen moves into the blood and carbon dioxide moves out. Just by living in these spaces the bacteria break them apart, but the immune response also causes significant damage leading to fluid accumulation in the lungs and pneumonia.
25-30% of all pneumonia patients develop pneumococcal bacteraemia. As there is a lot of blood circulating the lungs when it starts to break down the bacteria can gain entry into the blood pretty easily. This allows systemic distribution of the bacteria but the biggest problem is that it can lead to meningitis.
Pneumococcal meningitis develops in 15-20% of bacteraemic patients. Meningitis is inflammation of the brain and spinal cord’s protective coat, the meninges. Meningitis is fatal in 30% of cases but can also cause cognitive defects and hydrocephalus (water on the brain) which may lead to an increase in pressure on the brain resulting in further complications.
But we can (try and) deal with it
Over the years we have developed vaccines for the pneumococcus which have greatly enhanced our ability to combat this pathogen. Vaccine development also has an interesting history with some of the first ‘trials’ being performed directly onto human populations. In 1886 the English were mining gold in South Africa but were having trouble maintaining a workforce as the native South Africans lacked a history of exposure to the pneumococcus and the conditions in the mines (warm, damp, people close to one another for long periods of time) predisposed the area to major outbreaks. In 1911 the English brought in Sir Almroth Wright, renowned scientist in the area of typhoid vaccine research, to develop and test a pneumococcal vaccine in order to alleviate the burden of disease. Despite vaccinating over 50,000 miners and claiming his results showed that the vaccine worked, he was not fond of biostatistics and his data did not hold up well to scrutiny. This left him with the unfortunate nickname Sir Almost Right.
Many more pneumococcal vaccines have been tested since the mines in 1911 and now we have 2 commercially available vaccines, Pneumovax® and Prevenar®. Prevenar® is the more commonly used vaccine of the two due to its higher efficacy in the high risk groups for disease, the very young and very old.
Not Dealt With Yet
In spite of continued efforts over the last 130 years we are no closer to being able to claim victory over this highly successful pathogen. Vaccination lowered the numbers of cases of pneumococcal disease (both invasive and non-invasive) but has not affected its ability to live in a host without causing disease to the extent we had hoped. Antibiotics have helped treat those that have disease but there are problems with using them in cases of extreme disease (a whole other story for a new day). Despite these in-roads over 7 million cases of Otitis media, 200,000 cases of pneumonia and 6000 cases of meningitis are caused by the pneumococcus annually in the U.S.A. and still in Australia 1/8000 children will develop pneumococcal meningitis and suffer serious complications including death.
Due to this the next step in disease treatment and prevention is aimed at specific traits possessed by the pneumococcus rather than the broad spectrum approaches of the past. Current research into better vaccines, toxin neutralisation, and autolysis (causing the bacteria to kill itself) are all producing new and innovate options to help control this most dangerous pathogen.
In case you’re wondering what it is that I do exactly I am working on one of those alternative therapies I mentioned. It’s very early days but we have found that when a particular protein found in the pneumococcal membrane is mutated the bacterium has a hard time making a structure called the capsule. This is very important as the capsule is very important for that bacteria’s ability to survive inside you during disease (particularly in the blood). At this stage we are looking a properly characterising this protein but it is hoped in the future we could augment this protein in vivo and stop the bacteria in its tracks during disease, forcing it to alert itself to the immune system and subsequently be easily removed from the body.