Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.
Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.
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DOI：
10.1016/j.isci.2022.104862
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发表时间：
2022-09-16
期刊：
影响因子：
5.8
通讯作者：
Kumar, Ashok
中科院分区：
文献类型：
--
作者：
Das, Susmita;Singh, Sukhvinder;Satpathy, Sarthak;Bhasin, Manoj;Kumar, Ashok
眼部病原菌对抗生素耐药性的增加常常导致眼内炎等致盲性感染的治疗失败。因此，需要新的治疗方法来对抗耐多药感染。在这里，我们展示了一种药物再利用的方法，使用基于金黄色葡萄球菌（SA）感染小鼠视网膜的时间转录组学的连通性图。分析预测三种非抗生素药物，氯去qualinium chloride (DC), Clofilium tosylate （CT）和Glybenclamide （Glb）可以逆转SA感染特征。预测的药物在人视网膜细胞中对SA敏感和耐药菌株表现出抗炎特性。玻璃体内给药可减轻sa感染小鼠眼内炎症，DC和CT也可减轻细菌负担。药物治疗改善了视觉功能，同时减少了Caspase-3介导的视网膜细胞死亡。重要的是，所有药物都与万古霉素在改善疾病预后方面表现出协同作用。总的来说，我们的研究确定了三种非抗生素药物，并证明了它们在改善眼内细菌感染方面的治疗和预防效果。CMap分析预测三种药物可逆转金黄色葡萄球菌眼内炎的特征药物减轻MRSA和MSSA诱导的视网膜细胞炎症反应药物治疗改善实验性金黄色葡萄球菌眼内炎预测药物与抗生素药物具有辅助治疗潜力；微生物学;应用微生物学
Increasing antibiotic resistance among ocular pathogens often results in treatment failure for blinding infections such as endophthalmitis. Hence, newer therapeutics is needed to combat multidrug-resistant infections. Here, we show a drug repurposing approach using a connectivity map based on temporal transcriptomics of Staphylococcus aureus (SA) infected mouse retina. The analysis predicted three non-antibiotic drugs, Dequalinium chloride (DC), Clofilium tosylate (CT), and Glybenclamide (Glb) which reversed the SA infection signatures. Predicted drugs exhibited anti-inflammatory properties in human retinal cells against sensitive and resistant strains of SA. Intravitreal administration of all drugs reduced intraocular inflammation in SA-infected mouse eyes while DC and CT also reduced bacterial burden. Drug treatment improved visual function coinciding with reduced Caspase-3 mediated retinal cell death. Importantly, all drugs exhibited synergy with vancomycin in improving disease outcomes. Overall, our study identified three non-antibiotic drugs and demonstrated their therapeutic and prophylactic efficacies in ameliorating intraocular bacterial infection. CMap analysis predicted three drugs to reverse Staphylococcus aureus endophthalmitis signature Drugs attenuated MRSA and MSSA induced inflammatory response in retinal cells Drug treatment ameliorated experimental S. aureus endophthalmitis Predicted drugs exhibited adjunct therapeutic potential with antibiotic Medicine; Microbiology; Applied microbiology
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影响因子：
5.7
作者：
Das S;Singh S;Kumar A
通讯作者：
Kumar A
影响因子：
3.1
作者：
Callegan, MC;Booth, MC;Gilmore, MS
通讯作者：
Gilmore, MS
影响因子：
2.8
作者：
Hernandez-Camarena, Julio C.;Graue-Hernandez, Enrique O.;Bautista-de Lucio, Victor M.
通讯作者：
Bautista-de Lucio, Victor M.
视网膜中的免疫调节。
影响因子：
4.4
作者：
Detrick B;Hooks JJ
通讯作者：
Hooks JJ
DOI：
10.3390/pathogens4010111
发表时间：
2015-03-23
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Bispo PJ;Haas W;Gilmore MS
通讯作者：
Gilmore MS