Dataset Information

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

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 mutations in pmrB that promoted establishment and persistence of infection. Here we show that mutations in pmrB, which encodes the sensor kinase of the PmrAB two-component system, are acquired early in infection and increase resistance to the host antimicrobial lysozyme. Proteomic analysis of pmrB mutants reveal downregulation of proteins involved in LPS biosynthesis, antimicrobial resistance and phenazine production, 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 show enhanced adherence to airway epithelial cells and downregulate host CFTR expression. P. aeruginosa pmrB mutations are found in CF patient isolates and are associated with the same phenotypes, but are subject to an evolutionary trade-off: enhanced colonisation potential, resistance to host defences and CFTR inhibition, but concomitant increased susceptibility to antibiotics.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Pseudomonas Aeruginosa

DISEASE(S): Cystic Fibrosis

SUBMITTER: Stuart Armstrong

LAB HEAD: Julian A. Hiscox

PROVIDER: PXD009705 | Pride | 2018-07-11

REPOSITORIES: Pride

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			Action	DRS
	F017679.dat-pride.pride.mgf.gz	Mgf
	F017679.dat-pride.pride.mztab.gz	Mztab
	F017679.dat-pride.xml.gz	Xml
	F018409.dat-pride.pride.mgf.gz	Mgf
	F018409.dat-pride.pride.mztab.gz	Mztab

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

Bricio-Moreno Laura L Sheridan Victoria H VH Goodhead Ian I Armstrong Stuart S Wong Janet K L JKL Waters Elaine M EM Sarsby Joscelyn J Panagiotou Stavros S Dunn James J Chakraborty Adrita A Fang Yongliang Y Griswold Karl E KE Winstanley Craig C Fothergill Joanne L JL Kadioglu Aras A Neill Daniel R DR

Nature communications 20180706 1

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 ...[more]

PMID: 29980663

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