Targeting multidrug resistant <i>Staphylococcus</i> infections with bacterial histidine kinase inhibitors

Espinasse, Adeline; Goswami, Manibarsha; Yang, Jiacheng; Vorasin, Onanong; ji, yinduo; Carlson, Erin E.

doi:10.1039/d2sc05369a

Cited by 7 publications

(1 citation statement)

References 43 publications

(96 reference statements)

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“…Residual bacteria, harnessing signal transduction systems, such as the two-component system (TCS) and quorum sensing (QS), can rejuvenate biofilms, modulate drug efflux pumps, and bolster their drug resistance. [50][51][52][53][54] Their knack for birthing persister cells and regenerating biofilms is implicated in recurrent and lethal infections. Targeting the QS and TCS systems emerges as a promising strategy against biofilmcentric bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

Type I Photosensitizer Targeting Glycans: Overcoming Biofilm Resistance by Inhibiting the Two‐Component System, Quorum Sensing, and Multidrug Efflux

Xia,

Guo,

Zhao

et al. 2023

Advanced Materials

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Stubborn biofilm infections pose serious threats to human health due to the persistence, recurrence, and dramatically magnified antibiotic resistance. Photodynamic therapy has emerged as a promising approach to combat biofilm. Nevertheless, how to inhibit the bacterial signal transduction system and the efflux pump to conquer biofilm recurrence and resistance remains a challenging and unaddressed issue. Herein, we developed a boric acid‐functionalized lipophilic cationic type I photosensitizer, ACR‐DMP, which efficiently generates •OH to overcome the hypoxic microenvironment and photodynamically eradicates methicillin‐resistant Staphylococcus aureus (MRSA) and biofilms. Furthermore, it not only alters membrane potential homeostasis and osmotic pressure balance due to its strong binding ability with plasma membrane but also inhibits quorum sensing (QS) and the two‐component system (TCS), reduces virulence factors, and regulates the activity of the drug efflux pump attributed to the glycans targeting ability, helping to prevent biofilm recurrence and conquer biofilm resistance. In vivo, ACR‐DMP successfully obliterates MRSA biofilms attached to implanted medical catheters, alleviates inflammation, and promotes vascularization, thereby combating infections and accelerating wound healing. This work not only provides an efficient strategy to combat stubborn biofilm infections and bacterial multidrug resistance but also offers systematic guidance for the rational design of next‐generation advanced antimicrobial materials.This article is protected by copyright. All rights reserved

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Section: Introductionmentioning

confidence: 99%