Abstract

Several species of the Gram-negative genus Bordetella are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. Very recently, a novel atypical species, Bordetella pseudohinzii, was isolated from laboratory mice. These mice presented no obvious clinical symptoms but elevated numbers of neutrophils in bronchoalveolar lavage fluid and inflammatory signs in histopathology. We noted that this species can occur at high prevalence in a mouse facility despite regular pathogen testing according to the FELASA-recommendations. Affected C57BL/6 J mice had, in addition to the reported pulmonary alterations, tracheal inflammation with reduced numbers of ciliated cells, slower ciliary beat frequency, and largely (>50%) compromised cilia-driven particle transport speed on the mucosal surface, a primary innate defence mechanism. In an in vitro-model, Bordetella pseudohinzii attached to respiratory kinocilia, impaired ciliary function within 4 h and caused epithelial damage within 24 h. Regular testing for this ciliotropic Bordetella species and excluding it from colonies that provide mice for lung research shall be recommended. On the other hand, controlled colonization and infection with Bordetella pseudohinzii may serve as an experimental model to investigate mechanisms of mucociliary clearance and microbial strategies to escape from this primary innate defence response.

Highlights

  • Several Bordetella species are the cause of respiratory infections in mammals and birds, including whooping cough in humans

  • A high prevalence of disturbed tracheal particle transport speed (PTS) emerged in September 2016, and we began to subject samples of all animals used for experiments addressing pulmonary structure and function to microbiological diagnosis

  • Reference based SNP analysis indicated that all four isolates were highly related to B. pseudohinzii 8–296–03 compared to B. hinzii LMG 13501 (Supplementary Fig. 1a)

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Summary

Introduction

Several Bordetella species are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. In the course of experiments designed to study the mechanisms that regulate mucociliary clearance, a mechanism that eliminates inhaled particles from the airways, we encountered single murine tracheas with unusually low cilia-driven particle transport speed (PTS) This was observed both at baseline and after stimulation with acetylcholine and ATP, known activators of ciliary beat frequency (CBF)[15]. Affected mice present extensive airway inflammation with epithelial remodelling and functional impairment of clearance mechanisms We feel it justified to recommend regular testing for this Bordetella species and aiming to exclude it from facilities that provide mice for experimental lung research. On the other hand, controlled colonization and infection with B. pseudohinzii may serve as a model to investigate mechanisms of mucociliary clearance

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