Temporal Transcriptome Analysis Suggests Modulation of Key Pathways and Hub Genes in a Mice Model of Multi-Drug Resistant (MDR) Pseudomonas aeruginosa Endophthalmitis.
{"title":"Temporal Transcriptome Analysis Suggests Modulation of Key Pathways and Hub Genes in a Mice Model of Multi-Drug Resistant (MDR) <i>Pseudomonas aeruginosa</i> Endophthalmitis.","authors":"Poonam Naik, Joveeta Joseph","doi":"10.1080/02713683.2022.2124276","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Increasing incidence of multidrug-resistant <i>Pseudomonas aeruginosa</i> (<i>MDR-PA</i>) causing endophthalmitis challenges our ability to manage this vision-threatening condition. In this study, temporal dynamics of immune response in a mouse model of <i>MDR-PA</i> endophthalmitis was investigated by whole transcriptome analysis.</p><p><strong>Methods: </strong>C57BL/6 mice were infected with <i>MDR-PA</i> and antibiotic susceptible <i>(S-PA)</i> clinical strains and disease severity were monitored at 6 and 24-h postinfection (p.i), following which eyeballs were enucleated. Microarray analysis was performed using SuperPrint G3 Mouse Gene Expression v2 chip and the differential gene expression analysis was performed with limma package in R (v4.0.0.)/Bioconductor (v3.11).</p><p><strong>Results: </strong>Histopathological analysis revealed a significant difference in retinal architecture and vitreous infiltrates at 6 and 24 h. In comparison to <i>S-PA</i>, <i>MDR-PA</i> revealed altered expression of 923 genes at 6 h and 2220 genes at 24 h. Further, 23 and 76% of these altered genes and its downstream interacting proteins showed time-specific expression (6 and 24 h respectively), indicating their association with disease progression. At 24 hours, <i>MDR-PA</i> induced endophthalmitis showed aberrant immune response with the enrichment inflammasome signalling, dysregulated ubiquitination, complement cascade, MMPs NF-κβ and IL-1 signalling.</p><p><strong>Conclusion: </strong>The rapid development of transcriptional differences between the two-time points reveals that distinct genes contribute to disease severity. The results from this study highlighted a link between innate and adaptive immune responses and provided novel insights in the pathogenesis of <i>MDR-PA</i> endophthalmitis by extending the number of molecular determinants and functional pathways that underpin host-associated damage.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Eye Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/02713683.2022.2124276","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 1
Abstract
Purpose: Increasing incidence of multidrug-resistant Pseudomonas aeruginosa (MDR-PA) causing endophthalmitis challenges our ability to manage this vision-threatening condition. In this study, temporal dynamics of immune response in a mouse model of MDR-PA endophthalmitis was investigated by whole transcriptome analysis.
Methods: C57BL/6 mice were infected with MDR-PA and antibiotic susceptible (S-PA) clinical strains and disease severity were monitored at 6 and 24-h postinfection (p.i), following which eyeballs were enucleated. Microarray analysis was performed using SuperPrint G3 Mouse Gene Expression v2 chip and the differential gene expression analysis was performed with limma package in R (v4.0.0.)/Bioconductor (v3.11).
Results: Histopathological analysis revealed a significant difference in retinal architecture and vitreous infiltrates at 6 and 24 h. In comparison to S-PA, MDR-PA revealed altered expression of 923 genes at 6 h and 2220 genes at 24 h. Further, 23 and 76% of these altered genes and its downstream interacting proteins showed time-specific expression (6 and 24 h respectively), indicating their association with disease progression. At 24 hours, MDR-PA induced endophthalmitis showed aberrant immune response with the enrichment inflammasome signalling, dysregulated ubiquitination, complement cascade, MMPs NF-κβ and IL-1 signalling.
Conclusion: The rapid development of transcriptional differences between the two-time points reveals that distinct genes contribute to disease severity. The results from this study highlighted a link between innate and adaptive immune responses and provided novel insights in the pathogenesis of MDR-PA endophthalmitis by extending the number of molecular determinants and functional pathways that underpin host-associated damage.
期刊介绍:
The principal aim of Current Eye Research is to provide rapid publication of full papers, short communications and mini-reviews, all high quality. Current Eye Research publishes articles encompassing all the areas of eye research. Subject areas include the following: clinical research, anatomy, physiology, biophysics, biochemistry, pharmacology, developmental biology, microbiology and immunology.