In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation

Abstract Hyperinflammation elicited by lipopolysaccharide (LPS) that derives from multidrug‐resistant Gram‐negative pathogens, leads to a sharp increase in mortality globally. However, monotherapies aiming to neutralize LPS often fail to improve the prognosis. Here, an all‐in‐one drug delivery strat...

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Main Authors: Xiaoyu Li, Shaoqi Qu, Xiangbin Song, Congming Wu, Jianzhong Shen, Kui Zhu
Format: Article
Language:English
Published: Wiley 2023-09-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202302950
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author Xiaoyu Li
Shaoqi Qu
Xiangbin Song
Congming Wu
Jianzhong Shen
Kui Zhu
author_facet Xiaoyu Li
Shaoqi Qu
Xiangbin Song
Congming Wu
Jianzhong Shen
Kui Zhu
author_sort Xiaoyu Li
collection DOAJ
description Abstract Hyperinflammation elicited by lipopolysaccharide (LPS) that derives from multidrug‐resistant Gram‐negative pathogens, leads to a sharp increase in mortality globally. However, monotherapies aiming to neutralize LPS often fail to improve the prognosis. Here, an all‐in‐one drug delivery strategy equipped with bactericidal activity, LPS neutralization, and detoxification is shown to recognize, kill pathogens, and attenuate hyperinflammation by abolishing the activation of LPS‐triggered acute inflammatory responses. First, bactericidal colistin results in rapid bacterial killing, and the released LPS is subsequently sequestered. The neutralized LPS is further cleared by acyloxyacyl hydrolase to remove secondary fatty chains and detoxify LPS in situ. Last, such a system shows high efficacy in two mouse infection models challenged with Pseudomonas aeruginosa. This approach integrates direct antibacterial activity with in situ LPS neutralizing and detoxifying properties, shedding light on the development of alternative interventions to treat sepsis‐associated infections.
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spelling doaj.art-28dabe9881e14835b19e582a1146617b2023-09-15T09:28:59ZengWileyAdvanced Science2198-38442023-09-011026n/an/a10.1002/advs.202302950In Situ Neutralization and Detoxification of LPS to Attenuate HyperinflammationXiaoyu Li0Shaoqi Qu1Xiangbin Song2Congming Wu3Jianzhong Shen4Kui Zhu5National Key Laboratory of Veterinary Public Health Security College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health Security College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health Security College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health Security College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health Security College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health Security College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaAbstract Hyperinflammation elicited by lipopolysaccharide (LPS) that derives from multidrug‐resistant Gram‐negative pathogens, leads to a sharp increase in mortality globally. However, monotherapies aiming to neutralize LPS often fail to improve the prognosis. Here, an all‐in‐one drug delivery strategy equipped with bactericidal activity, LPS neutralization, and detoxification is shown to recognize, kill pathogens, and attenuate hyperinflammation by abolishing the activation of LPS‐triggered acute inflammatory responses. First, bactericidal colistin results in rapid bacterial killing, and the released LPS is subsequently sequestered. The neutralized LPS is further cleared by acyloxyacyl hydrolase to remove secondary fatty chains and detoxify LPS in situ. Last, such a system shows high efficacy in two mouse infection models challenged with Pseudomonas aeruginosa. This approach integrates direct antibacterial activity with in situ LPS neutralizing and detoxifying properties, shedding light on the development of alternative interventions to treat sepsis‐associated infections.https://doi.org/10.1002/advs.202302950acyloxyacyl hydrolaseantibioticdelivery systemslipopolysaccharide
spellingShingle Xiaoyu Li
Shaoqi Qu
Xiangbin Song
Congming Wu
Jianzhong Shen
Kui Zhu
In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation
Advanced Science
acyloxyacyl hydrolase
antibiotic
delivery systems
lipopolysaccharide
title In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation
title_full In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation
title_fullStr In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation
title_full_unstemmed In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation
title_short In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation
title_sort in situ neutralization and detoxification of lps to attenuate hyperinflammation
topic acyloxyacyl hydrolase
antibiotic
delivery systems
lipopolysaccharide
url https://doi.org/10.1002/advs.202302950
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AT congmingwu insituneutralizationanddetoxificationoflpstoattenuatehyperinflammation
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