Pathogenic Mannheimia haemolytica invades differentiated bovine airway epithelial cells

Cozens, D., Sutherland, E., Lauder, M., Taylor, G., Berry, C. C. and Davies, R. L. (2019) Pathogenic Mannheimia haemolytica invades differentiated bovine airway epithelial cells. Infection and Immunity, (doi:10.1128/IAI.00078-19) (PMID:30962401) (Early Online Publication)

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Abstract

The Gram-negative bacterium Mannheimia haemolytica is the primary bacterial species associated with bovine respiratory disease (BRD) which is responsible for significant economic losses to the livestock industries worldwide. Healthy cattle are frequently colonised by commensal serotype A2 strains, but disease is usually caused by pathogenic strains of serotype A1. For reasons that are poorly understood, a transition occurs within the respiratory tract and a sudden explosive proliferation of serotype A1 bacteria leads to the onset of pneumonic disease. Very little is known about the interactions of M. haemolytica with airway epithelial cells of the respiratory mucosa which might explain the different abilities of serotype A1 and A2 strains to cause disease. In the present study, host-pathogen interactions in the bovine respiratory tract were mimicked using a novel differentiated bovine bronchial epithelial cell (BBEC) infection model. In this model, differentiated BBECs were inoculated with serotype A1 or A2 strains of M. haemolytica and the course of infection followed over a five-day period by microscopic assessment and measurement of key proinflammatory mediators. We have demonstrated that serotype A1, but not A2, M. haemolytica invades differentiated BBECs by transcytosis and subsequently undergoes rapid intracellular replication before spreading to adjacent cells and causing extensive cellular damage. Our findings suggest that the explosive proliferation of serotype A1 M. haemolytica that occurs within the bovine respiratory tract prior to the onset of pneumonic disease is potentially due to bacterial invasion of, and rapid proliferation within, the mucosal epithelium. The discovery of this previously unrecognised mechanism of pathogenesis is important because it will allow the serotype A1-specific virulence determinants responsible for invasion to be identified and thereby provide opportunities for the development of new strategies for combatting BRD aimed at preventing early colonisation and infection of the bovine respiratory tract.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davies, Dr Robert and Berry, Dr Catherine and Lauder, Mr Miquel and Cozens, Mr Daniel and Sutherland, Miss Erin
Authors: Cozens, D., Sutherland, E., Lauder, M., Taylor, G., Berry, C. C., and Davies, R. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:08 April 2019
Copyright Holders:Copyright © 2019 Cozens et al.
First Published:First published in Infection and Immunity 2019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
630331Development of a three-dimensional air-liquid interface epithelial cell model to study pathogen interactions within the bovine respiratory tractRobert DaviesNational Centre for the Replacement of Animals Research (NC3RS)NC/L000822/1III - BACTERIOLOGY