Reduced fitness and enhanced immunogenicity ofural family isolates limit global spread.

INTRODUCTION: Lineage 4 (L4) includes the globally widespread Haarlem family and the geographically restricted Ural family, the latter primarily found north of the Black Sea. The biological basis for their differing global distributions remains unclear.

MATERIALS AND METHODS: We compared phenotypic characteristics of 12 genetically unlinked clinical isolates-six each from the Haarlem and Ural families-collected from individual patients in Poland. Growth kinetics, competitive fitness, intracellular replication in macrophages, hypoxia recovery, and host immune responses were evaluated usingassays.

RESULTS: Ural isolates exhibited significantly slower growth and lower colony-forming units in competitive fitness assays compared to Haarlem isolates. In macrophage infection models, Ural strains showed impaired intracellular replication. Additionally, Ural isolates demonstrated a diminished capacity to resuscitate from hypoxia, indicating possible defects in dormancy recovery. Host immune assays revealed that Ural isolates induced higher levels of IL-12p40, suggesting stronger immune activation.

DISCUSSION: Our findings indicate that Ural isolates possess reduced growth fitness and increased immunogenicity compared to Haarlem isolates. These traits may limit their capacity for transmission and persistence in hosts, potentially explaining their restricted geographic distribution.

CONCLUSION: The study highlights the influence ofgenetic background on host-pathogen interactions and epidemiological success.