Rethinking the pathogenesis of pyometra as a continuum model

Canine pyometra is a common, potentially fatal uterine infection whose pathogenesis remains incompletely resolved. We synthesise fifteen years of experimental and observational work integrating bacterial genetics, biofilm phenotype, host transcriptomics and novel in vitro models to propose a continuum model of disease. Escherichia coli isolates from canine uteri carried a higher burden of recognised uropathogenic virulence factors than rectal strains. Adhesin dependence varied markedly between strains: some lost >99% endometrial binding after fimH disruption, whereas others retained substantial binding capacity despite multi gene inactivation, implying redundant adhesion mechanisms. In vitro biofilm screening found biofilm formation in more uterine than faecal strains. In a larger cohort (27 pyometra cases, 45 control dogs) strong biofilm production was observed in uterine and vaginal isolates but not in control rectal isolates. Biofilm associated bacteria displayed markedly increased antimicrobial tolerance in vitro. Host transcriptomics revealed pronounced, stage specific modulation of innate immune genes, including a ∼100 fold elevation of endometrial canine beta defensin-1 mRNA in simulated dioestrus. Together, these data support a model in which varying combinations of host susceptibility and bacterial virulence, with biofilm formation as a plausible mechanism for persistence and recrudescence, underlie the clinical pyometra. Longitudinal genomic confirmation and in vivo evaluation of biofilm targeted interventions are priorities for future studies.