Effects of Fluticasone Propionate on Klebsiella pneumoniae and Gram-Negative Bacteria Associated with Chronic Airway Disease.
Effects of Fluticasone Propionate on Klebsiella pneumoniae and Gram-Negative Bacteria Associated with Chronic Airway Disease.
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吸入性皮质类固醇(ICS)通常是哮喘和慢性阻塞性肺疾病(COPD)的一线治疗处方。最近的证据表明，ICS的使用与呼吸道微生物群的变化有关，这可能会影响临床结果，如COPD患者肺炎的潜在风险增加。虽然皮质类固醇的免疫调节作用已得到广泛认可，但ICS是否能直接影响呼吸道细菌的行为尚不清楚。在这项初步研究中，我们探索了氟替卡松对呼吸道细菌的影响，这是一种常用的吸入皮质类固醇，重点放在肺炎克雷伯菌上，这是一种以前与慢性阻塞性肺疾病的氟替卡松相关肺炎有关的物种。我们观察到氟替卡松对肺炎克雷伯菌以及从哮喘患者分离的其他细菌的生长反应有显著的影响。氟替卡松暴露的肺炎克雷伯菌表现出多种细菌基因的表达改变，并降低了支气管上皮细胞的代谢活性及其人β-防御素 2的表达。靶向试验从氟替卡松暴露的肺炎克雷伯菌细胞中鉴定出一种氟替卡松代谢物，表明该物种可能能够代谢氟替卡松。总之，这些观察结果支持这样的假设，即呼吸道微生物区系的特定成员拥有在其微环境中响应或潜在利用皮质类固醇的功能谱系。这些发现为ICS的潜在直接影响的新研究方向奠定了基础，ICS通常是长期给患者开的，对更广泛的呼吸道微生物群落以及与哮喘和COPD结果有关的特定微生物物种的行为影响。吸入性皮质类固醇广泛用于治疗许多呼吸系统疾病，包括哮喘和慢性阻塞性肺病。虽然皮质类固醇对许多患者有益，但也可能产生负面影响。一些患者在治疗后没有好转，甚至出现了不良副作用。最近的研究表明，吸入皮质类固醇会改变人类呼吸道的细菌组成。然而，这些药物是否能直接影响这些细菌的行为尚不清楚。在这里，我们探讨了丙酸氟替卡松对肺炎克雷伯菌和其他感兴趣的呼吸道细菌的影响，包括从成人哮喘患者分离的主要细菌。我们提供了在培养中直接接触氟替卡松的生长反应的证据，并进一步检测了氟替卡松对肺炎克雷伯菌的影响，包括基因表达的变化和氟替卡松暴露的细菌对呼吸道细胞的影响。这些发现表明人类呼吸道细菌群落成员具有对糖皮质激素反应的功能能力，这可能对临床观察到的治疗反应的异质性有一定的意义。
Inhaled corticosteroids (ICS) are commonly prescribed first-line treatments for asthma and chronic obstructive pulmonary disease (COPD). Recent evidence has shown that ICS use is associated with changes in the airway microbiome, which may impact clinical outcomes such as potential increased risk for pneumonia in COPD. Although the immunomodulatory effects of corticosteroids are well appreciated, whether ICS could directly influence the behavior of respiratory tract bacteria has been unknown. In this pilot study we explored the effects of fluticasone proprionate, a commonly prescribed inhaled corticosteroid, on respiratory bacteria with an expanded focus on Klebsiella pneumoniae, a species previously implicated in fluticasone-associated pneumonia in COPD. We observed significant effects of fluticasone proprionate on growth responses of K. pneumoniae, as well as other bacterial species isolated from asthmatic patients. Fluticasone-exposed K. pneumoniae displayed altered expression of several bacterial genes and reduced the metabolic activity of bronchial epithelial cells and their expression of human β-defensin 2. Targeted assays identified a fluticasone metabolite from fluticasone-exposed K. pneumoniae cells, suggesting this species may be capable of metabolizing fluticasone proprionate. Collectively, these observations support the hypothesis that specific members of the airway microbiota possess the functional repertoire to respond to or potentially utilize corticosteroids in their microenvironment. These findings lay a foundation for novel research directions into the potential direct effects of ICS, often prescribed long term to patients, on the broader airway microbial community and on the behavior of specific microbial species implicated in asthma and COPD outcomes. IMPORTANCE Inhaled corticosteroids are widely prescribed for many respiratory diseases, including asthma and COPD. While they benefit many patients, corticosteroids can also have negative effects. Some patients do not improve with treatment and even experience adverse side effects. Recent studies have shown that inhaled corticosteroids can change the make-up of bacteria in the human respiratory tract. However, whether these medications can directly impact the behavior of such bacteria has been unknown. Here, we explored the effects of fluticasone propionate, a commonly prescribed inhaled corticosteroid, on Klebsiella pneumoniae and other airway bacteria of interest, including primary species isolated from adult asthma patients. We provide evidence of growth responses to direct fluticasone exposure in culture and further examined fluticasone’s effects on K. pneumoniae, including gene expression changes and effects of fluticasone-exposed bacteria on airway cells. These findings indicate that members of the human airway bacterial community possess the functional ability to respond to corticosteroids, which may have implications for the heterogeneity of treatment response observed clinically.
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DOI：
10.3390/ph3030514
发表时间：
2010-03-08
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Barnes PJ
通讯作者：
Barnes PJ
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1016/j.jaci.2020.03.028
发表时间：
2020-11
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Durack J;Christian LS;Nariya S;Gonzalez J;Bhakta NR;Ansel KM;Beigelman A;Castro M;Dyer AM;Israel E;Kraft M;Martin RJ;Mauger DT;Peters SP;Rosenberg SR;Sorkness CA;Wechsler ME;Wenzel SE;White SR;Lynch SV;Boushey HA;Huang YJ;National Heart, Lung, and Blood Institute’s ”AsthmaNet“
通讯作者：
National Heart, Lung, and Blood Institute’s ”AsthmaNet“
影响因子：
24.3
作者：
Crim, C.;Calverley, P. M. A.;Vestbo, J.
通讯作者：
Vestbo, J.
影响因子：
14.2
作者：
Abdel-Aziz, Mahmoud, I;Brinkman, Paul;Maitland-van der Zee, Anke H.
通讯作者：
Maitland-van der Zee, Anke H.