Asset Details
Do you wish to reserve the book?
Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy
Do you wish to request the book?
Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy
2022
Overview
Intestinal barrier derangement allows intestinal bacteria and their products to translocate to the systemic circulation.
Pseudomonas aeruginosa
(
PA
) superimposed infection in critically ill patients increases gut permeability and leads to gut-driven sepsis.
PA
infections are challenging due to multi-drug resistance (MDR), biofilms, and/or antibiotic tolerance. Inhibition of the quorum-sensing transcriptional regulator MvfR(PqsR) is a desirable anti-
PA
anti-virulence strategy as MvfR controls multiple acute and chronic virulence functions. Here we show that MvfR promotes intestinal permeability and report potent anti-MvfR compounds, the N-Aryl Malonamides (NAMs), resulting from extensive structure-activity-relationship studies and thorough assessment of the inhibition of MvfR-controlled virulence functions. This class of anti-virulence non-native ligand-based agents has a half-maximal inhibitory concentration in the nanomolar range and strong target engagement. Using a NAM lead in monotherapy protects murine intestinal barrier function, abolishes MvfR-regulated small molecules, ameliorates bacterial dissemination, and lowers inflammatory cytokines. This study demonstrates the importance of MvfR in
PA
-driven intestinal permeability. It underscores the utility of anti-MvfR agents in maintaining gut mucosal integrity, which should be part of any successful strategy to prevent/treat
PA
infections and associated gut-derived sepsis in critical illness settings. NAMs provide for the development of crucial preventive/therapeutic monotherapy options against untreatable MDR
PA
infections.
Pseudomonas aeruginosa
infections are increasingly difficult to treat due to the development of antimicrobial resistance. Here, the authors describe the synthesis, characterisation and efficacy of a quorum sensing inhibitor.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 14/19
/ 38
/ 49
/ 64
/ 64/60
/ 82/103
/ 82/51
/ Animals
/ Anti-Bacterial Agents - pharmacology
/ Anti-Bacterial Agents - therapeutic use
/ Bacterial Proteins - pharmacology
/ Biofilms
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Mucosa
/ Pseudomonas aeruginosa - physiology
/ Pseudomonas Infections - drug therapy
/ Pseudomonas Infections - microbiology
/ Science
/ Sepsis
