Polymyxin-based fluorescent probes to combat Gram-negative antimicrobial resistance

Reliable diagnostic approaches especially those targeting critical Gram-negative bacteria are urgently needed for the prevention of antimicrobial resistance. Polymyxin B (PMB) which specifically targets the outer membrane of Gram-negative bacteria is the last-line antibiotic against life-threatening...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Talanta (Oxford) 2023-08, Vol.260, p.124576-124576, Article 124576
Hauptverfasser: Han, Xiaowan, Cui, A-Long, Yang, He-Xian, Wu, Lingling, Wei, Rao, Liu, Qian, Li, Zhuo-Rong, Hu, Hai-Yu
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Reliable diagnostic approaches especially those targeting critical Gram-negative bacteria are urgently needed for the prevention of antimicrobial resistance. Polymyxin B (PMB) which specifically targets the outer membrane of Gram-negative bacteria is the last-line antibiotic against life-threatening multidrug-resistant Gram-negative bacteria. However, increasing number of studies have reported the spread of PMB-resistant strains. With the aim to specifically detect Gram-negative bacteria and potentially reduce the irrational use of antibiotics, we herein rationally designed two Gram-negative bacteria specific fluorescent probes based on our previous activity-toxicity optimization of PMB. The in vitro probe PMS-Dns showed fast and selective labeling of Gram-negative pathogens in complex biological cultures. Subsequently, we constructed the caged in vivo fluorescent probe PMS-Cy-NO2 by conjugating bacterial nitroreductase (NTR)-activatable positive charged hydrophobic near-infrared (NIR) fluorophore with polymyxin scaffold. Significantly, PMS-Cy-NO2 exhibited excellent Gram-negative bacterial detection capability with the differentiation between Gram-positive and Gram-negative in a mouse skin infection model. [Display omitted] •Two Polymyxin S-based imaging probes were constructed for fast and reliable diagnosing Gram-negative bacterial infections.•Gram-negative bacteria could be distinguished from gram-positive bacteria in vivo.•This imaging tool has potential in providing new insights to investigate mechanisms of PMXs resistance.
ISSN:0039-9140
1873-3573
DOI:10.1016/j.talanta.2023.124576