Persistent Bacterial Coinfection of a COVID-19 Patient Caused by a Genetically Adapted Pseudomonas aeruginosa Chronic Colonizer.
Persistent Bacterial Coinfection of a COVID-19 Patient Caused by a Genetically Adapted Pseudomonas aeruginosa Chronic Colonizer.
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DOI：
10.3389/fcimb.2021.641920
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发表时间：
2021
影响因子：
5.7
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Qu J;Cai Z;Liu Y;Duan X;Han S;Liu J;Zhu Y;Jiang Z;Zhang Y;Zhuo C;Liu Y;Liu Y;Liu L;Yang L
铜绿假单胞菌是一种可形成生物膜的机会致病菌，可引起免疫功能低下患者的慢性感染，并导致高死亡率。它被确定为COVID-19患者中常见的合并感染病原体，导致病情恶化。在我们医院，铜绿假单胞菌是COVID-19患者中发现的最常见的合并感染细菌之一。我们从一名严重的COVID-19患者中收集了一株强生物膜形成铜绿假单胞菌菌株，该菌株显示出小菌落变异形态。基因组和转录组测序分析与表型验证，以探讨其适应SARS-CoV-2感染的环境。基因组特征预测特定的基因组岛高度相关的毒力，转录调控和DNA限制修饰系统。表观遗传学分析揭示了一个特定的N6-甲基腺嘌呤（m6 A）甲基化模式，包括藻酸盐，鞭毛和群体感应相关基因的甲基化。差异基因表达分析表明，该分离物通过减少鞭毛形成（7.4 - 1，624.1倍）和过量产生胞外基质组分包括CdrA（4.4倍）、藻酸盐（5.2 - 29.1倍）和Pel（4.8-5.5倍）形成过量生物膜。总之，我们证明了具有新的表观遗传标记的铜绿假单胞菌临床分离株可以形成过度的生物膜，这可能会增强其抗生素耐药性和COVID-19患者的体内定植。
Pseudomonas aeruginosa is a biofilm-forming opportunistic pathogen which causes chronic infections in immunocompromised patients and leads to high mortality rate. It is identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness. In our hospital, P. aeruginosa is one of the top coinfecting bacteria identified among COVID-19 patients. We collected a strong biofilm-forming P. aeruginosa strain displaying small colony variant morphology from a severe COVID-19 patient. Genomic and transcriptomic sequencing analyses were performed with phenotypic validation to investigate its adaptation in SARS-CoV-2 infected environment. Genomic characterization predicted specific genomic islands highly associated with virulence, transcriptional regulation, and DNA restriction-modification systems. Epigenetic analysis revealed a specific N6-methyl adenine (m6A) methylating pattern including methylation of alginate, flagellar and quorum sensing associated genes. Differential gene expression analysis indicated that this isolate formed excessive biofilm by reducing flagellar formation (7.4 to 1,624.1 folds) and overproducing extracellular matrix components including CdrA (4.4 folds), alginate (5.2 to 29.1 folds) and Pel (4.8–5.5 folds). In summary, we demonstrated that P. aeuginosa clinical isolates with novel epigenetic markers could form excessive biofilm, which might enhance its antibiotic resistance and in vivo colonization in COVID-19 patients.