Type

Other / n/a

Authors

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

Subjects

Biochemistry

Topics
medical molecular biology pseudomonas aeruginosa menstrual cycle hydrogen peroxide follicular phase medical sciences cystic fibrosis luteal phase

Effect of Estrogen on Pseudomonas Mucoidy and Exacerbations in Cystic Fibrosis (2012)

Abstract 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 (PP. 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.)
Collections Ireland -> Royal College of Surgeons in Ireland -> Molecular Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular Medicine

Full list of authors on original publication

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

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
3
Brian J Harvey
Royal College of Surgeons in Ireland
Total Publications: 102
 
4
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
5
Cedric Gunaratnam
Royal College of Surgeons in Ireland
Total Publications: 18
 
6
Stephen Smith
Trinity College Dublin
Total Publications: 27
 
7
Sanjay H Chotirmall
Royal College of Surgeons in Ireland
Total Publications: 22