Genomic surveillance highlights the challenges posed by shape-shifting” strains

Genomic surveillance highlights the challenges posed by shape-shifting” strains

A groundbreaking genomic surveillance study has provided the clearest picture yet of the arms race between Streptococcus pneumoniae, the bacterium responsible for a range of diseases such as pneumonia and meningitis, and the vaccines developed to protect against the most dominant species. A strain called GPSC10 emerged as a particular threat due to its increased virulence, ability to change its structure to evade vaccines, and resistance to several common antibiotics.

The study, published today (August 16) in Lancet Microbe, was led 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 such as GPSC10.

Streptococcus pneumoniae, also known as pneumococcus, is a bacterial pathogen that causes illnesses ranging from ear infections to pneumonia, sepsis and meningitis. It is responsible for about nine million global infections annually, with older adults and children particularly vulnerable. More than 300,000 children die from pneumococcal infections each year, mostly in low- and middle-income countries (LMICs)1.

Since 2000, a series of pneumococcal conjugate vaccines (PCVs) targeting S. pneumoniae serotypes responsible for most cases of disease in infants have been used, leading to a reduction in cases worldwide. Currently, PCV-13 targets 13 serotypes, and PCVs targeting up to 25 serotypes are in development. However, there are more than 100 different serotypes that can affect children and adults in different ways. Knowing which serotypes are targeted by PCVs and what impact they are likely to have on the disease and the broader pneumococcal population is critical in developing effective global vaccination strategies.

The work of the GPS project since 2011 has built a picture of circulating S. pneumoniae serotypes, allowing trends in the bacterial population to be identified. One serotype, 24F, is on the rise, as documented by the National Pneumococcal Reference Center in France and many other countries such as Canada, Denmark, Germany, Israel, Italy, Japan, Lebanon, Norway, Spain and the United Kingdom.

In this new study, scientists at the Wellcome Sanger Institute performed whole-genome sequencing on 419 samples of S. pneumoniae serotype 24F collected between 2003 and 2018 from individuals in France by the National Pneumococcal Reference Center (NRCP) and the Association Clinique et Therapeutique Infantile du Val-de-Marne (ACTIV) and on 91 pneumococcal isolates of serotype 24F collected from individuals in Spain by the Hospital Sant Joan de Deu. To enable global comparison, an international collection of other S. pneumoniae genomes from the Global Pneumococcal Sequencing (GPS) project database was added.

In a microbiology laboratory, strain classification and drug resistance testing are 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 exchange. So it’s a test that can answer a lot of different questions.”

Dr. Stephanie Lo, lead author of the study, Wellcome Sanger Institute

The analysis showed that 24F was present in many countries primarily due to the distribution of three strains: GPSC10, GPSC16 and GPSC206. One strain in particular, GPSC10, was responsible for the rapid increase in 24F in France approximately 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 that showed 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 various countries. In India, the country estimated to have the highest burden of pneumococcal disease, researchers have predicted that GPSC10 has the potential to evade PCV-13. These and other studies from GPS partners around the world are summarized in an issue of Microbial Genomics.

Perhaps the biggest concern that emerged from the study was GPSC10's ability to express 17 different serotypes, only six of which are included in current PCV vaccines.

Dr. Emmanuelle Varon, a 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. Surveillance of pneumococcal disease, as carried out in France since 2001, is our best tool to assess the impact of vaccination policy 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. If a tribe dies out because it was attacked by a vaccine, other tribes may rise to take its place. A strain can also develop to the point where vaccines lose their effectiveness. What's important is that vaccine manufacturers and public health organizations have the best information with which to keep pace and ultimately save lives.

Professor Stephen Bentley, a senior author of the study from the Wellcome Sanger Institute, said: "It is exciting that genomic surveillance is now allowing us to make a real impact on improving pneumococcal vaccines and, crucially, helping to reduce the number of children dying from related diseases in low- and middle-income countries. The entire consortium of the Global Pneumococcal Survey should also be proud of the tremendous collaborative effort that went into generating this data.”

Source:

Wellcome Trust Sanger Institute

Reference:

Lo, SW, et al. (2022) Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study. The lancet microbe. doi.org/10.1016/S2666-5247(22)00158-6.

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