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International genomics study identifies emerging multidrug-resistant Streptococcus pneumoniae strain

Written by Miyako Rogers, Science Writer

A new study published in The Lancet has used whole-genome analysis of Streptococcus pneumoniae to identify a new “shape-shifting” strain called GPSC10 . Researchers found that GPSC10 is not only multi-drug-resistant but is also responsible for the rapid spread of serotype 24F, which causes a particularly deadly form of meningitis. This study is a part of the international Global Pneumococcal Sequencing Project, which aims to “establish a worldwide genomic surveillance network of Streptococcus pneumoniae” to inform public health policy and vaccine design.

A global health problem

Streptococcus pneumoniae infection can cause diseases such as meningitis, pneumonia and septicaemia. Every year around 9 million S. pneumoniae infections occur and over 300,000 children die from S. pneumoniae infection every year. To combat this global issue, pneumococcal conjugate vaccines (PCVs) have been in development since the year 2000. These vaccines target specific S. pneumoniae serotypes, groups of S. pneumoniae that exhibit specific surface proteins. The latest PCV that is publicly available is PCV-13, which targets 13 different serotypes responsible for many of the disease cases seen in children. PCVs targeting up to 25 different serotypes are in development, but there are over 100 distinct serotypes which have been shown to affect children and adults in a multitude of different ways.

GPSC10: A multi-drug resistant virulent strain

24F is a serotype that is not targeted by PCV-13 and, as a result, has been on the rise across the globe, identified in France, Canada, Denmark, Japan, Lebanon, and more. 24F is highly invasive and often fatal: In France, the mortality rate for meningitis due to 24F was 13% (between 2001-2016). 24F has also been shown to be resistant to antibiotics, such as penicillin. Moreover, PCVs currently in development (PCV15, PCV20, PCV 24) do not target this serotype. To address this issue, this study used whole-genome sequencing to pinpoint which S. pneumoniae strains are behind the spread of 24F and identified three strains: GPSC10, GPSC16, and GPSC206 (see Figure 1).

Figure 1 ¦ Prevalence of Streptococcus pneumoniae lineages by clinical manifestations and likelihood to cause (A) widespread invasive diseases and (B) meningitis.

Whole-genome sequencing was performed on over 400 samples of S. pneumoniae serotype 24F. Of the three strains identified, GPSC10 was found to be the main driver of infection (see Figure 1). All 24F isolates were clustered around the GPSC10 lineage, and researchers could trace the transmission of GPSC10 from Europe to other continents across the globe. Researchers also showed that GPSC10 took 3-5 years to spread across France and that this spread spiked after the introduction of PCV-13. In other words, this indicates due to evolutionary pressures caused by PCV-13, prevalence of the GPSC10 strain increased in S. pneumoniae population. GPSC10 was also shown to be the only strain that exhibited shape-shifting properties. GPSC10 is able to express 17 different serotypes and is, therefore, multi-drug and antibiotic-resistant. Moreover, only 6 of the 17 GPSC10 serotypes are targeted by current PVCs, so this strain also evades protection from current vaccines.

Using genomics to inform public health strategies

Genomics studies and international collaborations such as this study are essential for optimising public health strategies and vaccine design. This study also gives us insights into which serotypes to target and clues as to what impact emerging serotypes will have on disease outcomes. As new strains of S. pneumoniae evolve and existing strains become resistant to vaccines, the evolutionary arms race between S. pneumoniae and vaccine development is an ever-present struggle. The need for genomics research to combat this challenge is explained best by Professor Stephen Bentley, a senior author of the study, who notes, “It’s exciting that genomic surveillance now allows us to have a real impact on improving pneumococcal vaccines and, most importantly, helping to reduce the number of children who die from related illnesses in low- and middle-income countries.”

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Epidemiology / Genomics / Infectious Disease