Pan-Genome-Wide Association Study Identifies Genetic Factors Associated with the Pathogenicity of Invasive Serotype 19F Streptococcus Pneumoniae

Xing Shi,1,* Sandip Patil,2,* Qiuwei Yi,1,* Zihao Liu,1 Heping Wang,1 Chunqing Zhu,1 Yunsheng Chen,3 Yuejie Zheng,1 Shaowei Dong,2 Yanmin Bao1 1Department of Respiratory Medicine, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Clinical Microbiology Laboratory, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanmin Bao, Email [email protected] Shaowei Dong, Email [email protected]: Streptococcus pneumoniae is a common respiratory pathogen that poses significant health concerns in children, particularly serotype 19F strains that demonstrate high level of invasiveness in China. To investigate the genetic variations associated with high invasiveness of serotype 19F S. pneumoniae strains isolated from children in Shenzhen.Methods: We compared the genomic profiles of 42 invasive and 162 noninvasive strains from children’s respiratory tracts and employed pan-genome-wide association methods to elucidate the origins of genetic variation.Results: Significant gene presence variability was observed between invasive and noninvasive strains, suggesting a genetic basis for their pathogenicity differences. Invasive 19F strains demonstrated enhanced adhesion in co-culture experiments with human epithelial cells, with adhesion abilities correlating with the presence of specific genes. Despite high non-susceptibility to common antibiotics across all strains, no significant differences in antimicrobial susceptibility patterns were found between invasive and noninvasive groups.Conclusion: Although genomic differences within serotype 19F were relatively minor, invasive and noninvasive strains exhibited significant differences in adherence and invasiveness in the host microenvironment. While the underlying regulatory mechanisms remain uncertain, genetic differences play a crucial role in determining the invasiveness of S. pneumoniae serotype 19F strains in children.Keywords: pneumococcus, serotype 19F, invasive strains, pan-GWAS, genetic variation