Emergence of multidrug-resistant ST876 serotype 14 Streptococcus pneumoniae with spontaneous mutations driving pathogenesis: genomic and clinical insights from pneumococcal pericarditis and global screening

Background Streptococcus pneumoniae pericarditis is rare and lethal, yet how the pathogen evolves within the host during blood-to-pericardium spread remains unknown. Methods Two ST876 serotype 14 strains, hz23B (blood) and hz23P (pericardial effusion), were isolated from one purulent pericarditis patient. We determined antimicrobial susceptibility test (AST) by broth microdilution, performed whole-genome sequencing and mutation detection, multi-locus sequencing typing, and phylogenetic analysis against 1429 global serotype 14 genomes, modeled protein structures for unique mutations, and quantified growth under anaerobic/low-nutrient conditions, plus adherence and invasion on nasopharyngeal and lung epithelial cell lines. Results Both isolates showed an identical AST profile, where a multidrug-resistant phenotype was observed. Genomes differed by only 36 SNPs, while hz23P acquired CiaH_W192L (transmembrane kinase loss) and FabT_E21A (DNA-binding reduction). These changes conferred hz23P’s enhanced growth in THY and BSA+G under anaerobic stress ( p < 0.0001) but significantly reduced adherence ( p < 0.0001) and invasiveness ( p < 0.01) compared with hz23B. Global screening identified ST876 as a unique clone that carries pericarditis-linked mutations and successfully dominated China due to multidrug resistance. Conclusions We provide the first real-time evidence that ST876 serotype 14 pneumococci evolve within the host to survive the pericardial environment by attenuating virulence and energy. The global screen underscores the urgent need for surveillance targeting this multidrug-resistant and virulent clone.