MicrobiologyBytes

Pneumococcal diseases are a major public health problem all over the world. They are caused by the bacterium Streptococcus pneumoniae (or “pneumococcus”), a Gram-positive encapsulated coccus (a round bacterium). One of its most notable features is the presence of an external polysaccharide capsule. In this week’s podcast, I describe recent advances in vaccines against this organisms, and a very recent discovery.

Based on differences in the composition of the capsule, about different 90 serotypes have been identified. This capsule is an essential virulence factor since it acts as a protective coating to allow the bacterium to escape the immune system. Pneumococci are transmitted by direct contact with respiratory secretions from both patients and from seemingly healthy carriers.
When most healthy people are exposed to pneumococci, they may colonize the nose but not cause any symptoms. In a proportion of the bacteria spread to the sinuses or the middle ear, or infect the blood.
Serious invasive pneumococcal infections include pneumonia, meningitis and fever. Other common non-invasive diseases associated with this organism include otitis media (earache), sinusitis and bronchitis. At least a million children die of pneumococcal disease every year, most of them very young children in developing countries. In the developed world, the elderly persons carry the major burden of disease.
Compared with invasive disease, the non-invasive manifestations are usually less severe, but much more common. In the United States alone, 7 million cases of otitis media are attributed to pneumococci each year. Although all age groups may be affected, the highest rate of pneumococcal disease occurs in young children and in the elderly population. In developing countries infants under three months of age are at particularly high risk, especially for pneumococcal meningitis.
The World Health Organization says that acute respiratory infections kill an estimated 2.6 million children under five years of age annually, and pneumococcus causes over one million of these deaths, most of which occur in developing countries. Here the pneumococcus is probably the most important pathogen of early infancy. In Europe and the United States, pneumococcal pneumonia is the most common community-acquired bacterial pneumonia, and is estimated to affect approximately 100 in 100,000 adults each year. The corresponding figures for febrile bacteraemia and meningitis are 15–20 per 100,000 and 1–2 per 100,000, respectively.
The risk of all of these diseases is much higher in infants and elderly people. Even in economically developed regions, invasive pneumococcal disease carries high mortality. For adults with pneumococcal pneumonia the mortality rate is around 10%–20%, while it may exceed 50% in high-risk groups such as the elderly. Pneumonia is by far the most common cause of pneumococcal death worldwide.
Pneumococcal meningitis is also extremely nasty. Up to half of people who are infected are left with permanent after effects, which can include brain damage, paralysis or deafness.
The majority of pneumococcal disease in infants is associated with a small number of these serotypes, which may vary by region. The 11 most common serotypes of Streptococcus pneumoniae cause at least 75% of invasive infections.
Pneumococcal resistance to antibiotics is a serious and rapidly growing problem worldwide. Vaccination is the only effective tool to prevent pneumococcal disease.
The previous pneumococcal vaccine was based on the 23 most common serotypes, against which it had overall protection of about 60%–70%. Children under two years of age, and people with immunodeficiencies, for example HIV infection, did not consistently develop immunity following vaccination, so reducing the protective value of the vaccine for some major target groups who really need protection.
Following extensive clinical trials, a new generation of pneumococcal vaccines was developed. These are protein-polysaccharide combinations, known as conjugate vaccines, and contain between 7–11 carefully selected polysaccharides bound to a carrier protein. These are much more effective than the previous vaccine and even give protection in children under two years of age.
The new vaccine has been available in the USA for about five years, but is only just being rolled out in the UK now. This is in spite of the fact that pneumococcal disease affects 400 children in the UK each year, kills 50 and leaving many others disabled.
Shamefuly, the main reason for the delayed was one of cost. The new vaccine costs £33 a shot, which is more than all the other childhood vaccines put together.

• Pneumococcal Conjugate Vaccine – USA
• Pneumococcal Conjugate Vaccine – UK

Here at the University of Leicester we’ve had a research interest in Streptococcus pneumoniae for many years, so I’d like to discuss about a paper recently published by my colleagues Aras Kadioglu and Peter Andrew, who teach on the Microbiology and Biological Sciences degree courses here (Oggioni M.R. et al. Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis. Molecular Microbiology. 2006 61: 1196-1210). The authors measured gene expression in Streptococcus pneumoniae cells in the blood and in tissues such as the brain and lung of mice.
Despite its importance as a pathogen, relatively little is known about the pathology of pneumococcal diseases. In particular, what makes the organism shift from harmlessly colonizing the nose and throat to invading the blood and lungs is not understood. Neither is how pneumococcus is able to cross the blood–brain barrier to cause meningitis.
Using the highly sensitive technique of real-time PCR in a Light Cycler machine, they showed that different genes are expressed when the organisms are in the blood and when solid tissues are colonized. From this discovery, they went on to build a model system to compare pneumococci growing planktonically in liquid cultures, and as a biofilm attached to a surface. The upshot of this is that these differences appear to be controlled by a protein known as competence stimulating peptide or CSP.
When the CSP receptor was mutated, the organism was unable to form a biofilm on a solid surface.
CSP is what is known as a quorum-sensing peptide, a system by which bacteria are able to talk to each other by means of signaling models, and so appear to act co-ordinately as one mass rather than as single cells.
Now, quorum-sensing is a big and very important topic in microbiology, so I’ll come back to in next week’s podcast.
The importance of these finding is a much better understanding of the pathogenesis of pneumococcal diseases, as well as a potential route to treat these serious infections by interfering with quorum-sensing.

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This entry was posted on Monday, September 18th, 2006 at 11:29 am and is filed under Bacteria, Health, Medicine, Microbiology, Podcast, Science. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.