中文版 | English
Title

Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells

Author
Corresponding AuthorLi, Jian
Publication Years
2023-02-01
DOI
Source Title
ISSN
2079-6382
Volume12Issue:2
Abstract
Polymyxins are last-line antibiotics for the treatment of Gram-negative 'superbugs'. However, nephrotoxicity can occur in up to 60% of patients administered intravenous polymyxins. The mechanisms underpinning nephrotoxicity remain unclear. To understand polymyxin-induced nephrotoxicity, human renal proximal tubule cells were treated for 24 h with 0.1 mM polymyxin B or two new analogues, FADDI-251 or FADDI-287. Transcriptomic analysis was performed, and differentially expressed genes (DEGs) were identified using ANOVA (FDR < 0.2). Cell viability following treatment with polymyxin B, FADDI-251 or FADDI-287 was 66.0 +/- 5.33%, 89.3 +/- 3.96% and 90.4 +/- 1.18%, respectively. Transcriptomics identified 430, 193 and 150 DEGs with polymyxin B, FADDI-251 and FADDI-287, respectively. Genes involved with metallothioneins and Toll-like receptor pathways were significantly perturbed by all polymyxins. Only polymyxin B induced perturbations in signal transduction, including FGFR2 and MAPK signaling. SIGNOR network analysis showed all treatments affected essential regulators in the immune system, autophagy, cell cycle, oxidative stress and apoptosis. All polymyxins caused significant perturbations of metal homeostasis and TLR signaling, while polymyxin B caused the most dramatic perturbations of the transcriptome. This study reveals the impact of polymyxin structure modifications on transcriptomic responses in human renal tubular cells and provides important information for designing safer new-generation polymyxins.
Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
Others
Funding Project
Australian National Health and Medical Research Council (NHMRC)[APP1104581]
WOS Research Area
Infectious Diseases ; Pharmacology & Pharmacy
WOS Subject
Infectious Diseases ; Pharmacology & Pharmacy
WOS Accession No
WOS:000938149000001
Publisher
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/502129
DepartmentShenzhen People's Hospital
Affiliation
1.Monash Univ, Monash Biomed Discovery Inst, Infect Program, Melbourne, Vic 3800, Australia
2.Monash Univ, Dept Microbiol, Melbourne, Vic 3800, Australia
3.Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, Parkville, Vic 3052, Australia
4.Southern Univ Sci & Technol, Clin Med Coll Jinan Univ 2, Shenzhen Peoples Hosp, Dept Crit Care Med,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
5.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
6.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin 300308, Peoples R China
First Author AffilicationShenzhen People's Hospital
Recommended Citation
GB/T 7714
Li, Mengyao,Azad, Mohammad A. K.,Thompson, Philip E.,et al. Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells[J]. Antibiotics-Basel,2023,12(2).
APA
Li, Mengyao.,Azad, Mohammad A. K..,Thompson, Philip E..,Roberts, Kade D..,Velkov, Tony.,...&Li, Jian.(2023).Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells.Antibiotics-Basel,12(2).
MLA
Li, Mengyao,et al."Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells".Antibiotics-Basel 12.2(2023).
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