Zoonotic Bordetella bronchiseptica infection at the swine-human interface: unveiling the evolutionary path from an animal to a human pathogen

TL;DR

A swine Bordetella infection evolved to infect humans by integrating and then discarding a plasmid, enhancing its virulence and adaptability.

Contribution

Discovery of a 'capture-and-discard' plasmid integration mechanism enabling host adaptation and increased pathogenicity in B. bronchiseptica.

Findings

Human-adapted B. bronchiseptica RL57 integrates and discards a plasmid, retaining virulence genes while eliminating replicative burden.

Plasmid loss rewires bacterial metabolism, enhancing biofilm formation, thermotolerance, and hypervirulence in human hosts.

Proposed One Health surveillance triad to monitor plasmid-chromosome dynamics and metabolic shifts for zoonotic risk mitigation.

Abstract

Bordetella bronchiseptica, long regarded as a veterinary pathogen, is now emerging as a zoonotic threat to humans, particularly in immunocompromised individuals. We report a sentinel event involving a synchronized B. bronchiseptica outbreak in swine and their human caretaker, providing a unique opportunity to examine cross-species transmission and adaptation at the genomic level. Comparative genomics revealed that the human-adapted isolate (RL57) and its swine progenitor (XX35) share an identical chromosome, with XX35 harbouring an extra conjugative plasmid. Remarkably, RL57 did not simply lose this plasmid; instead, the entire plasmid was integrated into the chromosome via site-specific recombination. This integration allowed permanent retention of plasmid-encoded virulence and fitness genes, after which the plasmid was discarded to eliminate its replicative burden – a “capture-and-discard” mechanism of evolution. Following plasmid loss, the RL57 strain exhibited hypervirulence, faster growth, enhanced thermotolerance, and increased biofilm formation, indicating successful adaptation to the human host. Plasmid loss paradoxically rewired bacterial metabolism: sulfur assimilation and sulfonate utilization pathways were upregulated to fuel host adaptation. Strikingly, despite a collapse in transcription of specific metabolic modules, translational compensation maintained high protein levels, driving robust biofilm formation and thermal tolerance. These findings reveal a previously unrecognized evolutionary strategy in which plasmid integration followed by subsequent plasmid loss amplifies pathogenicity and host adaptability. Finally, we propose a One Health surveillance triad – metagenomic tracking of plasmid–chromosome dynamics, recombination hotspot screening, and metabolic shift monitoring – to proactively identify and mitigate such zoonotic events.

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