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Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis

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).

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).

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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


Local EPrints ID: 340876
PURE UUID: b70ca88c-a583-45ce-ad99-bfaac9d3f7e1

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

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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

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