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A Supramolecular Antibiotic Targeting Drug-Resistant Pseudomonas aeruginosa through the Inhibition of Virulence Factors and Activation of Acquired Immunity.
- Source :
-
ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 Aug 14; Vol. 16 (32), pp. 41828-41842. Date of Electronic Publication: 2024 Aug 01. - Publication Year :
- 2024
-
Abstract
- The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHP <superscript>plus</superscript> , which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa . Furthermore, dHTSN1@pHP <superscript>plus</superscript> was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHP <superscript>plus</superscript> exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa -infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHP <superscript>plus</superscript> in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa .
- Subjects :
- Animals
Mice
Adaptive Immunity drug effects
Microbial Sensitivity Tests
Humans
Drug Resistance, Bacterial drug effects
Mice, Inbred BALB C
Female
Pseudomonas aeruginosa drug effects
Pseudomonas aeruginosa pathogenicity
Anti-Bacterial Agents pharmacology
Anti-Bacterial Agents chemistry
Virulence Factors
Pseudomonas Infections drug therapy
Pseudomonas Infections immunology
Pseudomonas Infections microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1944-8252
- Volume :
- 16
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- ACS applied materials & interfaces
- Publication Type :
- Academic Journal
- Accession number :
- 39088848
- Full Text :
- https://doi.org/10.1021/acsami.4c06665