# High-resolution genomics uncovers region-specific evolution and virulence of ocular Streptococcus pneumoniae

## TL;DR

This study uses high-resolution genomics to uncover unique traits of eye-infecting Streptococcus pneumoniae in China, highlighting region-specific adaptations and potential targets for better treatments.

## Contribution

The first high-resolution genomic analysis of ocular S. pneumoniae in Asia reveals region-specific genetic features linked to UV adaptation and virulence.

## Key findings

- Chinese ocular pneumococci lack the zmpC virulence gene and carry the ermB resistance gene instead of mefA.
- Asian isolates show unique SNPs and mosaic blocks in uvrB and SP_0338, linked to UV damage repair and DNA integrity.
- The DNA integrity gene SP_1247 is globally conserved and essential for ocular S. pneumoniae survival.

## Abstract

Streptococcus pneumoniae is the leading cause of sight-threatening ocular infection. However, comprehensive molecular epidemiological analyses that focus on ocular pneumococci are limited. We performed a high-resolution whole-genome analysis (WGS) of ocular pneumococcal isolates from the Zhejiang province of China and a global data set (n = 58). Using latex agglutination and the Quellung reaction, nine serotypes were identified, with PCV13 covering 54.5% of the Chinese isolates, and no non-typeable (NT) strains were found in conjunctivitis. Illumina short-read data were assembled de novo and submitted for resistance and virulence gene BLAST, phylogenetic analysis, recombination prediction, and single-nucleotide polymorphism (SNP) analysis. Phylogenetically, the Chinese isolates showed a sporadic distribution. All Chinese strains carried the ermB gene for macrolide resistance, rather than mefA, in strains from Western countries. Virulence gene analysis revealed that no zmpC gene was identified in Chinese pneumococcal strains associated with keratitis and conjunctivitis. A marked accumulation of SNPs and mosaic blocks in Asian isolates is strongly associated with the acquisition of region-specific alleles encoding the ATP-dependent protease SP_0338 and the UV-damage repair enzyme uvrB. Interestingly, the DNA integrity gene SP_1247 has emerged as a globally conserved and functionally essential determinant of ocular S. pneumoniae. These findings underscore that genes involved in DNA integrity surveillance and UV stress response are enriched for non-synonymous mutations and might be a virulence prerequisite for pneumococci colonizing the UV-exposed ocular surface. Such features should guide the development of vaccines, antibiotics, and diagnostics for pneumococcal eye infections.

Due to the lack of studies focusing on ocular pneumococcus other than in the United States, little is known about the molecular epidemiology of S. pneumoniae, which causes ocular infections in other regions worldwide. This study provides the first high-resolution genomic map of ocular S. pneumoniae, revealing Asian-specific variability in UV-damage repair (uvrB) and global DNA integrity (SP_1247) genes that may be essential for survival on UV-exposed ocular surfaces. By linking ermB-driven macrolide resistance, the absence of zmpC, and unique serotype and recombination distribution to these UV-adaptation signatures, this work redefines ocular pneumococci as a distinct ecotype whose regional evolution must be incorporated into future vaccines, antibiotic guidelines, and rapid molecular diagnostics to prevent blindness-causing eye infections.