A landmark genomic surveillance study has provided the clearest picture yet of the arms race between them Streptococcus pneumoniae, the bacterium responsible for a number of diseases such as pneumonia and meningitis, and the vaccines developed to protect against the most common types. One strain called GPSC10 proved to be a particular threat due to its increased virulence, ability to alter its structure to evade vaccines, and resistance to several common antibiotics.
The study published today (16 August) in Lancet Microbe, was conducted by the Wellcome Sanger Institute, National Reference Center for Pneumococci, France, and Hospital Sant Joan de Deu, Spain, as part of the Global Pneumococcal Sequencing (GPS) project. The results demonstrate the value of genomic surveillance to inform vaccine design and highlight the challenge posed by ‘shape-shifting’ strains like GPSC10.
Streptococcus pneumoniae, also known as pneumococcus, is a bacterial pathogen that causes diseases ranging from ear infections to pneumonia, blood poisoning and meningitis. It is responsible for about nine million global infections annually, with older adults and children being particularly susceptible. More than 300,000 children die from pneumococcal infection each year, mostly in low- and middle-income countries (LMICs).1.
Since 2000, a number of pneumococcal conjugate vaccines (PCVs) have been used in a targeted manner S. pneumoniae Serotypes responsible for most cases of illness in infants2, leading to a reduction in disease worldwide. Currently, PCV-13 targets 13 serotypes, and PCVs targeting up to 25 serotypes are under development. However, there are more than 100 different serotypes that can affect children and adults in different ways. Knowing which serotypes are targeted by PCV and what impact they are likely to have on the disease and the broader pneumococcal population is crucial in developing effective global vaccination strategies.
Through the work of the GPS project, since 2011 an image of the S. pneumoniae Circulating serotypes have been constructed that allow trends in the bacterial population to be identified. One serotype, 24F, is on the rise as documented by the National Reference Center for Pneumococci in France and many other countries including Canada, Denmark, Germany, Israel, Italy, Japan, Lebanon, Norway, Spain and the UK.
In this new study, scientists at the Wellcome Sanger Institute performed whole genome sequencing on 419 samples from S. pneumoniae Serotype 24F collected from individuals in France between 2003 and 2018 by the National Reference Center for Pneumococci (NRCP) and the Association Clinique et Therapeutique Infantile du Val-de-Marne (ACTIV), and on 91 pneumococcal isolates of serotype 24F collected by Individuals in Spain from Sant Joan de Deu Hospital. To allow global comparison, an international collection is presented by others S. pneumoniae genomes were added from the Global Pneumococcal Sequencing (GPS) project database.
dr Stephanie Lo, first author of the study from the Wellcome Sanger Institute, said: “In a microbiology laboratory, strain classification and drug resistance testing is time-consuming and resource-intensive. Whole genome sequencing can now reliably infer serotypes and antibiotic resistance profiles, identify where outbreaks might occur and track which strains mediate serotype switching. So it’s a test that can answer a lot of different questions.”
Analysis showed that 24F was present in many countries mainly due to the spread of three strains: GPSC10, GPSC16 and GPSC206. One strain in particular, GPSC10, was responsible for the rapid increase in 24F in France about four years after the introduction of PCV-13. It has been found to have high disease potential and is resistant to multiple antibiotic treatments.
These results support recent research showing that GPSC10 drove the increase in 24F following the introduction of PCV-13 in Spain and that 24F is one of the most common causes of pneumococcal disease in children in different countries. In India, the country estimated to have the greatest burden of pneumococcal disease, researchers have predicted that GPSC10 has the potential to bypass PCV-13. This and other studies from GPS partners around the world are collected in an issue of Microbial Genomics.
Perhaps the biggest concern arising from the study was GPSC10’s ability to express 17 different serotypes, only six of which are present in current PCV vaccines.
dr Emmanuelle Varon, senior author of the study from the National Reference Center for Pneumococci, Center Hospitalier Intercommunal de Créteil, France, said: “The Streptococcus pneumoniae Strain GPSC10 is something of a shapeshifter, capable of expressing a wide range of serotypes and multidrug resistance patterns. Pneumococcal disease surveillance, as carried out in France since 2001, is our best tool to assess the impact of vaccination policies and will allow us to detect the emergence of other non-vaccine serotypes.”
To some extent, the evolutionary arms race between pathogens and vaccine makers is inevitable. When a tribe dies out because it was attacked by a vaccine, other tribes can rise up to take its place. A strain can also develop to the point where vaccines lose their effectiveness. Importantly, vaccine manufacturers and public health organizations have the best information to keep up with and ultimately save lives.
Professor Stephen Bentley, a senior author on the study from the Wellcome Sanger Institute, said: “It is exciting that genomic surveillance is now enabling us to have a real impact on improving pneumococcal vaccines and, importantly, helping to reduce the number reduce the number of children dying from related diseases in low- and middle-income countries. The entire Global Pneumococcal Survey consortium should also be proud of the tremendous collective effort that has gone into generating this data.”
dr Matthew Midgley
Welcome Sanger Institute
Cambridge, CB10 1SA
Telephone: 0044 1223 494856
Notes for editors:
1 More information about S. pneumoniae and pneumococcal disease can be found on the CDC website.
2 A serotype is a group of strains that share similar biological characteristics, usually on the cell surface. in the S. pneumoniaethe serotype is definitely by properties of the capsule that surrounds the bacterium and protects it from attack by the host’s immune system. A vaccine that targets a specific serotype is capable of destroying all associated strains.
Stephanie W Lo and Kate Mellor et al. (2022). Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae Lineage mediates serotype replacement after PCV13: an international whole genome sequencing study. Lancet Microbe. DOI: https://doi.org/10.1016/S2666-5247(22)00158-6
This research was funded by the Bill & Melinda Gates Foundation, the Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention (CDC).
The Global Pneumococcal Sequencing (GPS) Project
The mission of the GPS is to provide a worldwide genomic surveillance network for the Streptococcus pneumoniae Providing evidence of pneumococcal disease control by building a decentralized system for local data generation and analysis that will continue to be sustainable in the future. https://www.pneumogen.net/gps/
The Wellcome Sanger Institute
The Wellcome Sanger Institute is a world-leading genomics research center. We conduct large-scale research that forms the basis of knowledge in biology and medicine. We are open and cooperative; Our data, results, tools and technology are shared worldwide to advance science. Our ambition is great – we take on projects that are not possible elsewhere. We harness the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the frontiers of genomics. Our findings are used to improve health and understand life on earth. Find out more at www.sanger.ac.uk or follow us TwitterFacebook, LinkedIn and on our blog.
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The Lancet Microbe
subject of research
The emergence of a multiresistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole genome sequencing study
Article publication date
August 16, 2022