Abstract
BackgroundDespite a significant global burden of disease, there is still no vaccine against shigellosis widely available. One aim of the European Union funded STOPENTERICS consortium is to develop vaccine candidates against Shigella. Given the importance of translational vaccine coverage, here we aimed to characterise the Shigella strains being used by the consortium by whole genome sequencing, and report on the stability of strains cultured in different laboratories or through serial passage.MethodsWe sequenced, de novo assembled and annotated 20 Shigella strains being used by the consortium. These comprised 16 different isolates belonging to 7 serotypes, and 4 derivative strains. Derivative strains from common isolates were manipulated in different laboratories or had undergone multiple passages in the same laboratory. Strains were mapped against reference genomes to detect SNP variation and phylogenetic analysis was performed.ResultsThe genomes assembled into similar total lengths (range 4.14–4.83 Mbp) and had similar numbers of predicted coding sequences (average of 4,400). Mapping analysis showed the genetic stability of strains through serial passages and culturing in different laboratories, as well as varying levels of similarity to published reference genomes. Phylogenetic analysis revealed the presence of three main clades among the strains and published references, one containing the Shigella flexneri serotype 6 strains, a second containing the remaining S. flexneri serotypes and a third comprised of Shigella sonnei strains.ConclusionsThis work increases the number of the publically available Shigella genomes available and specifically provides information on strains being used for vaccine development by STOPENTERICS. It also provides information on the variability among strains maintained in different laboratories and through serial passage. This work will guide the selection of strains for further vaccine development.
Highlights
Despite a significant global burden of disease, there is still no vaccine against shigellosis widely avail‐ able
Derivative strains from the same isolate, but manipulated in different laboratories of the STOPENTERICS consortium were denoted ‘_1’ and ‘_2’, whereas those that had undergone serial passage (~10 passages)
The work presented here increases the number of publically available Shigella genomes, including for the first time, sequencing data for Shigella sonnei (Ss). sonnei 25931, two S. flexneri 1b, one S. flexneri 1a, one S. flexneri 3a and 8 S. flexneri six isolates
Summary
Despite a significant global burden of disease, there is still no vaccine against shigellosis widely avail‐ able. Given the importance of translational vaccine coverage, here we aimed to characterise the Shigella strains being used by the consortium by whole genome sequencing, and report on the stability of strains cultured in differ‐ ent laboratories or through serial passage. To assemble Shigella expertise to identify and rapidly take novel vaccine candidates through to clinical trials for effective vaccine development, the research is carried out among different academic institutions (e.g. University of Oxford, Wellcome Trust Sanger Institute, Institut Pasteur) and vaccines companies (Novartis Vaccines Institute for Global Health and Sanofi-Pasteur). To ensure the congruence of strains between laboratories, and create a public resource for vaccine development and further Shigella research, we whole genome sequenced the Shigella strains used by the STOPENTERICS consortium which are used as they offer most effective breadth of cross-protection against Shigella sp. We assessed the presence of SNPs between strains and against references, as well as defined their phylogenetic relationships, and compared genetic stability of strains maintained in different consortium laboratories and after serial passage
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