Biology subjects

Kandasamy, K.

Publications and source records attributed to Kandasamy, K..

3 recordsLinked to original sources

bioRxiv2021

A Comparative Genome-wide Transcriptome Analysis of Glucocorticoid Responder and Non-Responder Primary Human Trabecular Meshwork Cells

The genome-wide gene expression analysis of primary human trabecular meshwork (HTM) cells with known glucocorticoid (GC) responsiveness was not reported earlier. Therefore, the purpose of this study was to investigate genes and pathways involved in the GC responsiveness in human trabecular meshwork (HTM) cells using RNA sequencing. A perfusion cultured human anterior segment ex vivo model was utilized to identify the induction of GC-induced ocular hypertension in one eye of a paired eyes after dexamethasone treatment based on the maximum intraocular pressure response and in the contralateral eye, HTM cells were isolated to classify GC-responder and non-responder cells. Some previously reported and unique genes and their associated pathways were identified in HTM cells in response to dexamethasone treatment versus vehicle control and more significantly in GC-responder and non-responder cells. This study will open up the possibility of identifying suitable molecular targets which have the potential to treat GC-induced ocular hypertension/glaucoma.

genomics↗

bioRxiv2021

Comparative Analysis of non-coding small-RNAs in P. aeruginosa Keratitis Strains with Different Antibiotic Susceptibility

Pseudomonas aeruginosa, is a gram-negative bacterium causes opportunistic or nosocomial infections in immunocompromised individuals. In recent years, a steady increase in human corneal infections of P. aeruginosa has been reported with increased multi-drug resistance (MDR) or extensively drug resistance (XDR). Several non-coding sRNAs, has been identified to regulate various physiological processes in P. aeruginosa, including biofilm formation, quorum sensing. However, the regulatory mechanism of sRNAs in MDR/XDR pathways of P. aeruginosa keratitis strains is not yet studied. In this study, we identified bacterial sRNAs in publicly available P. aeruginosa keratitis genomes and investigated their regulatory role in MDR/XDR pathways using bioinformatic analysis. Totally, 46 P. aeruginosa keratitis strains from different geographical regions were included. Of 46, Eight (30%) out of Twenty-seven and Nine (52) out of Nineteen P. aeruginosa strains from India and Australia were identified as not-MDR. Whereas, 10 (38%) Indian and 9 (47%) Australian strains were identified as MDR. Eight Indian strains were identified as XDR. Out of 46 strains, 23 (50%) carried ExoU, 21(45%) carried ExoS and two (5%) strains carried both ExoU and ExoS, exotoxins for their virulence. The sRNA, SPA0021 was identified in 18 MDR/XDR and 6 not-MDR strains along with UCBPP-PA14. Interestingly, majority of the imipenem resistant P. aeruginosa keratitis strains from the present study was found to be carried SPA0023 sRNA (18 out of 30 strains). The outer membrane porin protein OprD, identified as binding target of SPA0023. Negative regulation or inactivation of OprD, reported in increased imipenem resistance in P. aeruginosa. Mutation analysis revealed that SPA0023 carrying P. aeruginosa keratitis strains contains a lesser number of amino acid changes in OprD protein than other strains. These findings indicate, imipenem resistance in SPA0023 carried strains might arose from the negative regulation or inhibition of OprD by SPA0023. However, functional studies are warranted with large number of P. aeruginosa keratitis strains to confirm the negative regulation of OprD by SPA0023 and imipenem resistance.

genomics↗

bioRxiv2020

Comparative genomics of ocular Pseudomonas aeruginosa strains from keratitis patients with different clinical outcomes

Bacterial keratitis caused by Pseudomonas aeruginosa is a destructive disease of cornea. Pseudomonas keratitis progresses rapidly and leads to vision loss if untreated. Even with adequate treatment, many patients show poor visual outcomes. The virulence factors or multiple drug-resistant (MDR) mechanisms of the ocular strains responsible for poor clinical outcomes remain largely unknown. Here, we performed whole-genome sequencing of five P. aeruginosa strains cultured from corneal scrapings of the healed and corneal buttons of the poor outcome keratitis patients. We investigated the distribution of virulence factors, resistance genes and resistance-associated mutations, the efflux-pump system in all five genomes, and as groups between poor and good clinical outcome as well as MDR vs. non-MDR. We detected several resistance genes and mutations associated with drug resistance in MDR groups; however, a large number of virulence genes were detected in all our genomes. Among the virulence genes, exoU and exoS exotoxin of the Type III secretion system detected in MDR and non-MDR strains, respectively, considered as main virulence contributors of keratitis pathogenesis. Despite this fact, this study did not show an association between MDR with exoU and poor clinical outcomes. However, strain-specific resistance and virulence genes were observed in this study, suggesting their role in the clinical outcome. Mainly, the flagellar genes fliC and fliD, reported to altering the host immune response, might impact the clinical outcome. This comparative study may provide new insights into the genome of ocular strains and requires further functional studies.

microbiology↗