The University of Southampton
University of Southampton Institutional Repository

Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis

Record type: Article

BACKGROUND: Women with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in disease severity.

METHODS: We evaluated the effects of estradiol and its metabolite estriol on P. aeruginosa in vitro and in vivo and determined the effect of estradiol on disease exacerbations in women with cystic fibrosis.

RESULTS: Estradiol and estriol induced alginate production in P. aeruginosa strain 01 and in clinical isolates obtained from patients with and those without cystic fibrosis. After prolonged exposure to estradiol, P. aeruginosa adopted early mucoid morphology, whereas short-term exposure inhibited bacterial catalase activity and increased levels of hydrogen peroxide, which is potentially damaging to DNA. Consequently, a frameshift mutation was identified in mucA, a key regulator of alginate biosynthesis in P. aeruginosa. In vivo levels of estradiol correlated with infective exacerbations in women with cystic fibrosis, with the majority occurring during the follicular phase (P<0.05). A review of the Cystic Fibrosis Registry of Ireland revealed that the use of oral contraceptives was associated with a decreased need for antibiotics. Predominantly nonmucoid P. aeruginosa was isolated from sputum during exacerbations in the luteal phase (low estradiol). Increased proportions of mucoid bacteria were isolated during exacerbations occurring in the follicular phase (high estradiol), with a variable P. aeruginosa phenotype evident in vivo during the course of the menstrual cycle corresponding to fluctuating estradiol levels.

CONCLUSIONS: Estradiol and estriol induced mucoid conversion of P. aeruginosa in women with cystic fibrosis through a mutation of mucA in vitro and were associated with selectivity for mucoid isolation, increased exacerbations, and mucoid conversion in vivo. (Funded by the Molecular Medicine Ireland Clinician-Scientist Fellowship Programme).

Full text not available from this repository.

Citation

Chotirmall, Sanjay H., Smith, Stephen G., Gunaratnam, Cedric, Cosgrove, Sonya, Dimitrov, Borislav D., O'Neill, Shane, Harvey, Brian J., Greene, Catherine M. and McElvaney, Noel G. (2012) Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis New England Journal of Medicine, 366, (21), pp. 1978-1986. (doi:10.1056/NEJMoa1106126). (PMID:22607135).

More information

e-pub ahead of print date: 20 May 2012
Published date: 24 May 2012
Additional Information: Free full text at doi:10.1056/NEJMoa1106126
Keywords: cystic fibrosis, pseudomonas aeruginosa
Organisations: Primary Care & Population Sciences

Identifiers

Local EPrints ID: 340876
URI: http://eprints.soton.ac.uk/id/eprint/340876
PURE UUID: b70ca88c-a583-45ce-ad99-bfaac9d3f7e1

Catalogue record

Date deposited: 16 Jul 2012 13:26
Last modified: 18 Jul 2017 05:41

Export record

Altmetrics

Contributors

Author: Sanjay H. Chotirmall
Author: Stephen G. Smith
Author: Cedric Gunaratnam
Author: Sonya Cosgrove
Author: Borislav D. Dimitrov
Author: Shane O'Neill
Author: Brian J. Harvey
Author: Catherine M. Greene
Author: Noel G. McElvaney

University divisions


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×