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Estrogen induced P. aeruginosa conversion in women with cystic fibrosis
Chotirmall SH. N Engl J Med. 2012;10.1056/NEJMa1106126.
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The estrogen hormone estradiol and its metabolite estriol triggered mucoid conversion of Pseudomonas aeruginosa in women with cystic fibrosis through a mutation of mucA in vitro and were associated with selectivity for fibroids, increased disease severity and mucoid conversion in vivo, according to the results of a recent study.
Researchers evaluated estradiol and estriol on P. aeruginosa in vitro and in vivo to determine estradiol’s effect on disease exacerbations in women with cystic fibrosis. During the 2-year prospective study in Dublin, Ireland, researchers recruited 44 women with 139 infective exacerbations. Estradiol and estriol induced alginate production in P. aeruginosa strain 01(PA01), which normally is nonmucoid at baseline, and also in clinical isolates from patients with and without cystic fibrosis. P. aeruginosa adopted early mucoid morphology following extended estradiol exposure, while short-term exposure decreased bacterial catalase activity and increased hydrogen peroxide levels. As a result of these increased levels, which can damage DNA, researchers identified a frameshift mutation in the mucA gene, a critical regulator of alginate biosynthesis in P. aeruginosa.
During the follicular phase of the patients’ menstrual cycles when estradiol levels peaked (P<.05), in vivo levels of estradiol correlated with infective exacerbations. Researchers also said the patients’ use of oral contraceptives was associated with a decreased need for antibiotic courses and a lower exacerbation rate.
Researchers said predominantly nonmucoid P. aeruginosa was isolated from sputum during exacerbations in the luteal phase when estradiol levels were low. Mucoid bacteria at higher levels were isolated during exacerbations that occurred during the follicular phase when a variable P. aeruginosa phenotype was evident in vivo during the menstrual cycle that corresponded to fluctuating estradiol levels.
“A significant relationship between exacerbations and estradiol levels was evident, with the majority of exacerbations occurring during the follicular phase,” researchers said. “Although oral contraceptives may be protective against [infective] exacerbations, a double blind, placebo-controlled study of [their use] in women with cystic fibrosis would be necessary to provide proof.”