Emergence of an East China lineage of Chlamydia psittaci with accelerated evolution and zoonotic potential: a multi-center, genomic epidemiological study

ABSTRACT Chlamydia psittaci is a zoonotic pathogen that can cause severe human respiratory infections. To assess its genetic diversity and zoonotic risk, we screened 1,525 samples from humans, poultry, and wild birds in East China (EC) during 2020–2023 and recovered 41 genomes using a targeted capture assay, together with 103 publicly available genomes. Phylogenomic analysis identified a distinct whole-genome lineage, designated the EC lineage, that was significantly enriched among human-derived isolates relative to other lineages. The EC lineage showed an elevated substitution rate, extensive recombination, and multiple Chlamydia abortus -like genomic regions, indicating a distinctive evolutionary history. Genetically linked poultry–human clusters were consistent with recent cross-host transmission, whereas the potential for human-to-human transmission remains unresolved. Strengthened genomic surveillance is warranted to monitor this lineage. IMPORTANCE Chlamydia psittaci is a bird-associated pathogen that can cause severe respiratory disease in humans, yet its local evolution and transmission between animals and humans remain poorly understood. Here, we identify a distinct lineage circulating mainly in East China that is disproportionately represented among human infections and is genetically linked to poultry isolates. This lineage also shows unusually extensive genomic change, including recombination and regions similar to those found in the related species Chlamydia abortus . These findings highlight poultry as an important interface for monitoring emerging C. psittaci lineages and demonstrate the value of genomic surveillance for detecting pathogen variants with increased relevance to human health. The study provides a framework for integrating animal and human surveillance within a One Health strategy.