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, Daniel R. Neill

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
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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.

Original languageEnglish
Article number2635
Number of pages12
JournalNature Communications
Volume9
Early online date6 Jul 2018
DOIs
Publication statusPublished - 2018

Keywords

  • Bacterial evolution
  • Bacterial genes
  • Bacterial host response
  • Bacterial pathogenesis

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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