Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa

Laura Bricio-Moreno, Victoria H. Sheridan, Ian Goodhead, Stuart Armstrong, Janet K.L. Wong, Elaine M. Waters, Joscelyn Sarsby, Stavros Panagiotou, James Dunn, Adrita Chakraborty, Yongliang Fang, Karl E. Griswold, Craig Winstanley, Joanne L. Fothergill (), Aras Kadioglu and Daniel R. Neill ()
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Laura Bricio-Moreno: University of Liverpool
Victoria H. Sheridan: University of Liverpool
Ian Goodhead: University of Salford
Stuart Armstrong: University of Liverpool
Janet K.L. Wong: University of Liverpool
Elaine M. Waters: University of Liverpool
Joscelyn Sarsby: University of Liverpool
Stavros Panagiotou: University of Liverpool
James Dunn: University of Liverpool
Adrita Chakraborty: University of Liverpool
Yongliang Fang: Thayer School of Engineering, Dartmouth
Karl E. Griswold: Thayer School of Engineering, Dartmouth
Craig Winstanley: University of Liverpool
Joanne L. Fothergill: University of Liverpool
Aras Kadioglu: University of Liverpool
Daniel R. Neill: University of Liverpool

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Pseudomonas aeruginosa colonises the upper airway of cystic fibrosis (CF) patients, providing a reservoir of host-adapted genotypes that subsequently establish chronic lung infection. We previously experimentally-evolved P. aeruginosa in a murine model of respiratory tract infection and observed early-acquired mutations in pmrB, encoding the sensor kinase of a two-component system that promoted establishment and persistence of infection. Here, using proteomics, we show downregulation of proteins involved in LPS biosynthesis, antimicrobial resistance and phenazine production in pmrB mutants, and upregulation of proteins involved in adherence, lysozyme resistance and inhibition of the chloride ion channel CFTR, relative to wild-type strain LESB65. Accordingly, pmrB mutants are susceptible to antibiotic treatment but show enhanced adherence to airway epithelial cells, resistance to lysozyme treatment, and downregulate host CFTR expression. We propose that P. aeruginosa pmrB mutations in CF patients are subject to an evolutionary trade-off, leading to enhanced colonisation potential, CFTR inhibition, and resistance to host defences, but also to increased susceptibility to antibiotics.

Date: 2018
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DOI: 10.1038/s41467-018-04996-x

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