Effect of Estrogen on Pseudomonas Mucoidy and Exacerbations in Cystic Fibrosis
Effect of Estrogen on Pseudomonas Mucoidy and Exacerbations in Cystic Fibrosis
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DOI：
10.1056/nejmoa1106126
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发表时间：
2012-05-24
影响因子：
158.5
通讯作者：
McElvaney, Noel G.
中科院分区：
文献类型：
--
作者：
Chotirmall, Sanjay H.;Smith, Stephen G.;McElvaney, Noel G.
背景：患有囊性纤维化的女性发生铜绿假单胞菌粘液转化的风险增加，这导致了疾病严重程度的性别二分法。方法在体外和体内评价雌二醇及其代谢物雌三醇对铜绿假单胞菌的影响，并确定雌二醇对囊性纤维化妇女疾病加重的影响。结果stradiol和雌三醇诱导铜绿假单胞菌01及囊性纤维化患者和非囊性纤维化患者临床分离株产生海藻酸盐。在长期暴露于雌二醇后，铜绿假单胞菌呈现早期粘液形态，而短期暴露抑制细菌过氧化氢酶活性并增加过氧化氢水平，过氧化氢对DNA有潜在损害。因此，在P. aeruginosa藻酸盐生物合成的关键调控因子mucA中发现了一个移码突变。体内雌二醇水平与囊性纤维化妇女感染加重相关，大多数发生在卵泡期(P
BackgroundWomen with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in disease severity.MethodsWe 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.ResultsEstradiol 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