Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy

Stephenson, Keith; Hoch, James A.

doi:10.1016/s0163-7258(02)00198-5

Cited by 96 publications

(125 citation statements)

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“…PmrA was activated by the phosphoryl analogue BeF 3 À , which has been used to activate the REC domain to determine its activated structure 19 . The pmra box on the pbgP promoter of Klebsiella pneumoniae was verified previously 20 , and a series of various-length DNAs covering the half-1 and half-2 sites were mixed with an equal amount of BeF 3 À -activated PmrA for co-crystallization (Supplementary Table 1) to obtain the crystals of complexes with 25-and 26-bp DNA (Supplementary Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…3). We reveal the crystal structures of BeF 3 À -activated PmrA in complex with 25-bp DNA at 3.2 Å resolution and with 26-bp DNA at 3.8 Å resolution (Table 1). The space group of the PmrA-25-bp DNA crystal is C222, with two copies of the protein-DNA complex (complex-1 and complex-2) in the asymmetric unit ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The interface between PmrA-1 and PmrA-2 is 1,336 Å 2 , with the two RECs contributing to 1,024 Å 2 . Each activated REC contains a five-stranded parallel b-sheet (b1-5) surrounded by five helices (a1-5) as well as a BeF 3 À non-covalently bounded to Asp 51 and a Mg 2 þ coordinated by BeF 3 À and carbonyl oxygen from the main chains and side chains of surrounding residues ( Supplementary Fig. 5a).…”

Section: Resultsmentioning

confidence: 99%

“…They are involved in a variety of processes, including virulence, antibiotic resistance and quorum sensing. TCSs are absent in mammals, so they are attractive targets for drug development 2,3 . The specific inhibitors of TCS systems are believed to work differently from conventional antibiotics and may be effective against various antibiotic-resistant bacteria 2,3 .…”

mentioning

confidence: 99%

“…TCSs are absent in mammals, so they are attractive targets for drug development 2,3 . The specific inhibitors of TCS systems are believed to work differently from conventional antibiotics and may be effective against various antibiotic-resistant bacteria 2,3 . Structural studies of TCSs that control virulence or antibiotic resistance, such as the PmrA/PmrB TCS 2 , are therefore crucial.…”

mentioning

confidence: 99%

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Structure and dynamics of the polymyxin-resistance-associated response regulator PmrA in complex with the promoter DNA

Hsiao¹

2016

Acta Cryst Sect A

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Structure and dynamics of the polymyxin-resistance-associated response regulator PmrA in complex with the promoter DNA

Hsiao¹

2016

Acta Cryst Sect A

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New Approaches to Understanding Bacterial Histidine Kinase Activity and Inhibition

Wilke

Carlson

2015

Kinomics

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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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Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy

Cited by 96 publications

References 89 publications

Structure and dynamics of the polymyxin-resistance-associated response regulator PmrA in complex with the promoter DNA

Structure and dynamics of the polymyxin-resistance-associated response regulator PmrA in complex with the promoter DNA

New Approaches to Understanding Bacterial Histidine Kinase Activity and Inhibition

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

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