Considerable efforts have been exerted to identify factors contributing to the success of epidemic Staphylococcus aureus clones, however, comparative phenotypic studies lack representation owing to the small number of strains. Large-scale strain collections focused on the description of genomic characteristics.

Small-colony variants (SCVs) of Staphylococcus aureus have drawn increasing research attention. Owing to their slow growth, atypical colony morphology, and unusual metabolic characteristics, SCVs often cause confusion in the laboratory.

Metagenomic next-generation sequencing (mNGS) is useful for difficult to cultivate pathogens. Here, we use cerebrospinal fluid mNGS to diagnose invasive meningococcal disease. The complete genome sequences of Neisseria meningitidis were assembled using N. meningitidis of ST4821-serotype C isolated from four patients. To investigate the phylogeny, 165 CC4821 N. meningitidis genomes from 1972 to 2017 were also included. The core genome accumulated variation at a rate of 4.84×10−8 substitutions/nucleotide site/year. CC4821 differentiated into four sub-lineages during evolution (A, B, C, and D). While evolving from sub-lineage A (early stage) to sub-lineage D (late stage), the ST and CC4821 serotype converged into the ST4821-serotype C clone. Most strains of sub-lineage D were isolated from invasive meningococcal disease, with increasing resistance to quinolones. Phylogeographic analysis suggests that CC4821 has spread across 14 countries. Thus, the selective pressure of quinolones may cause CC4821 to converge evolutionarily, making it more invasive and facilitating its spread.

Given the importance of metabolic adaptation during infection, new insights are required regarding the pathogenesis of S. aureus , particularly for epidemic clones. We accordingly investigated the role of metabolic determinants that are unique to the epidemic clones ST59 and ST398.

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