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烟曲霉可增强铜绿假单胞菌共培养物中弹性蛋白酶的产生。

Aspergillus fumigatus enhances elastase production in Pseudomonas aeruginosa co-cultures.

作者信息

Smith Karen, Rajendran Ranjith, Kerr Stephen, Lappin David F, Mackay William G, Williams Craig, Ramage Gordon

机构信息

Institute of Healthcare Associated Infection, School of Health, Nursing and Midwifery, University of the West of Scotland, United Kingdom.

Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom.

出版信息

Med Mycol. 2015 Sep;53(7):645-55. doi: 10.1093/mmy/myv048. Epub 2015 Jul 10.

Abstract

In the cystic fibrosis (CF) lung the presence of bacteria and fungi in the airways promotes an inflammatory response causing progressive lung damage, ultimately leading to high rates of morbidity and mortality. We hypothesized that polymicrobial interactions play an important role in promoting airway pathogenesis. We therefore examined the interplay between the most commonly isolated bacterial CF pathogen, Pseudomonas aeruginosa, and the most prevalent filamentous fungi, Aspergillus fumigatus, to test this. Co-culture experiments showed that in the presence of A. fumigatus the production of P. aeruginosa elastase was enhanced. This was confirmed by the presence of zones of clearance on Elastin-Congo Red (ECR) agar, which was identified as elastase by mass spectrometry. When P. aeruginosa were grown in a co-culture model with mature A. fumigatus biofilms, 60% of isolates produced significantly more elastase in the presence of the filamentous fungi than in its absence (P < .05). The expression of lasB also increased when P. aeruginosa isolates PA01 and PA14 were grown in co-culture with A. fumigatus. Supernatants from co-culture experiments were also significantly toxic to a human lung epithelial cell line (19-38% cell cytotoxicity) in comparison to supernatants from P. aeruginosa only cultures (P < .0001). Here we report that P. aeruginosa cytotoxic elastase is enhanced in the presence of the filamentous fungi A. fumigatus, suggesting that this may have a role to play in the damaging pathology associated with the lung tissue in this disease. This indicates that patients who have a co-colonisation with these two organisms may have a poorer prognosis.

摘要

在囊性纤维化(CF)患者的肺部,气道中细菌和真菌的存在会引发炎症反应,导致肺部进行性损伤,最终致使高发病率和高死亡率。我们推测,多种微生物之间的相互作用在促进气道发病机制中起着重要作用。因此,我们检测了最常见的CF病原菌铜绿假单胞菌与最普遍的丝状真菌烟曲霉之间的相互作用,以验证这一推测。共培养实验表明,在烟曲霉存在的情况下,铜绿假单胞菌弹性蛋白酶的产生会增加。这在弹性蛋白 - 刚果红(ECR)琼脂上出现的透明圈得到了证实,通过质谱鉴定该透明圈为弹性蛋白酶。当铜绿假单胞菌在与成熟的烟曲霉生物膜的共培养模型中生长时,60%的分离株在丝状真菌存在时产生的弹性蛋白酶明显多于不存在时(P < 0.05)。当铜绿假单胞菌分离株PA01和PA14与烟曲霉共培养时,lasB的表达也会增加。与仅铜绿假单胞菌培养的上清液相比,共培养实验的上清液对人肺上皮细胞系也具有显著毒性(细胞毒性为19 - 38%)(P < 0.0001)。在此我们报告,在丝状真菌烟曲霉存在的情况下,铜绿假单胞菌的细胞毒性弹性蛋白酶会增强,这表明其可能在该疾病中与肺组织相关的损伤病理过程中发挥作用。这表明同时感染这两种微生物的患者可能预后较差。

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