Two-component system GacS/GacA, a global response regulator of bacterial physiological behaviors

Song, Huihui; Li, Yuying; Wang, Yan

doi:10.1016/j.engmic.2022.100051

Cited by 24 publications

(18 citation statements)

References 163 publications

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“…Both QS and TCS are intricately linked with bacterial biofilm formation. [77][78][79] As depicted in the heatmap in Figure 7B, for the ACR-DMB group, genes related to osmotic pressure and oxidative stress saw increased expression, while those associated with TCS and virulence factors were down-regulated. This was because of the ACR-DMB anchored on the cell membrane through hydrophobic interaction and strong electrostatic interaction (two positive charges), which caused a significant imbalance in the bacterial cells' osmotic pressure, leading to the upregulation of multiple ion channel proteins.…”

Section: Mechanism Study Of the Enhanced Antibiofilm Ability Of Pssmentioning

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: Mechanism Study Of the Enhanced Antibiofilm Ability Of Pssmentioning

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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“…A. baumannii possesses several TCSs including AdeRS, BaeSR, PmrAB, GacSA, BfmRS, and A1S_2811 that were responsible to influence their pathogenic potentials ( De Silva & Kumar, 2019 ). Among these TCSs, the GacSA TCS was reported to play a significant role for cell growth and adaptation to complex environmental changes via regulates gene expression at the transcription and post-transcriptional levels ( Song, Li & Wang, 2023 ). Moreover, the GacSA TCS reported to be responsible in participating in biofilm formation in Pseudomonas aeruginosa.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of pellicle-forming ability in clinical carbapenem-resistant Acinetobacter baumannii

Puah

Teh

et al. 2023

PeerJ

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Background Acinetobacter baumannii was reported to have resistance towards carbapenems and the ability to form an air-liquid biofilm (pellicle) which contributes to their virulence. The GacSA two-component system has been previously shown to play a role in pellicle formation. Therefore, this study aims to detect the presence of gacA and gacS genes in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates recovered from patients in intensive care units and to investigate their pellicle forming ability. Methods The gacS and gacA genes were screened in 96 clinical CRAB isolates using PCR assay. Pellicle formation assay was performed in Mueller Hinton medium and Luria Bertani medium using borosilicate glass tubes and polypropylene plastic tubes. The biomass of the pellicle was quantitated using the crystal violet staining assay. The selected isolates were further assessed for their motility using semi-solid agar and monitored in real-time using real-time cell analyser (RTCA). Results All 96 clinical CRAB isolates carried the gacS and gacA genes, however, only four isolates (AB21, AB34, AB69 and AB97) displayed the ability of pellicle-formation phenotypically. These four pellicle-forming isolates produced robust pellicles in Mueller Hinton medium with better performance in borosilicate glass tubes in which biomass with OD570 ranging from 1.984 ± 0.383 to 2.272 ± 0.376 was recorded. The decrease in cell index starting from 13 hours obtained from the impedance-based RTCA showed that pellicle-forming isolates had entered the growth stage of pellicle development. Conclusion These four pellicle-forming clinical CRAB isolates could be potentially more virulent, therefore further investigation is warranted to provide insights into their pathogenic mechanisms.

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Section: Introductionmentioning

confidence: 99%

“…The GacS Multi-Kinase Network (MKN) regulates the planktonic-to-sessile switch (3,5). Several kinases, including GacS, PA1611 (PA14_43670), RetS, SagS, and NahK, signal in this network to regulate the activity of a post-transcriptional global regulator protein, RsmA (3,5). RsmA inhibits translation of mRNAs related to biofilm formation, quorum sensing (QS), pyocyanin (PYO) production, and type VI secretion systems, promoting the planktonic state (3,5).…”

Section: Introductionmentioning

confidence: 99%

“…Several kinases, including GacS, PA1611 (PA14_43670), RetS, SagS, and NahK, signal in this network to regulate the activity of a post-transcriptional global regulator protein, RsmA (3,5). RsmA inhibits translation of mRNAs related to biofilm formation, quorum sensing (QS), pyocyanin (PYO) production, and type VI secretion systems, promoting the planktonic state (3,5). RsmA is inactivated by the small regulatory RNAs, rsmY and rsmZ, which are transcribed in response to MKN activity (3,5).…”

Section: Introductionmentioning

confidence: 99%

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The histidine kinase NahK regulates pyocyanin production through the PQS system

Mendoza,

Guercio,

Smiley

et al. 2023

Preprint

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Many bacterial histidine kinases work in two-component systems that combine into larger multi-kinase networks. NahK is one of the kinases in the GacS Multi-Kinase Network (MKN), which is the MKN that controls biofilm regulation in the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa). This network has also been associated with regulating many virulence factors P. aeruginosa secretes to cause disease. However, the individual role of each kinase is unknown. In this study, we identify NahK as a novel regulator of the phenazine pyocyanin (PYO). Deletion of nahK led to a four-fold increase in PYO production, almost exclusively through upregulation of phenazine operon two (phz2). We determined that this upregulation is due to mis-regulation of all P. aeruginosa quorum sensing systems, with a large upregulation of the Pseudomonas quinolone signal (PQS) system and a decrease in production of the acyl-homoserine lactone-producing system, las. In addition, we see differences in expression of quorum sensing inhibitor proteins that align with these changes. Together, this data contributes to understanding how the GacS MKN modulates QS and virulence.

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Two-component system GacS/GacA, a global response regulator of bacterial physiological behaviors

Cited by 24 publications

References 163 publications

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

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

Characterisation of pellicle-forming ability in clinical carbapenem-resistant Acinetobacter baumannii

The histidine kinase NahK regulates pyocyanin production through the PQS system

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