Pyrogallol downregulates the expression of virulence-associated proteins in Acinetobacter baumannii and showing anti-infection activity by improving non-specific immune response in zebrafish model

Acinetobacter baumannii, a virulent uropathogen with widespread antibiotic resistance, has arisen as a critical scientific challenge, necessitating the development of innovative therapeutic agents. This is the first study reveal the proteomic changes in A. baumannii upon pyrogallol treatment for und...

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Veröffentlicht in:International journal of biological macromolecules 2023-01, Vol.226, p.853-869
Hauptverfasser: Abirami, Gurusamy, Alexpandi, Rajaiah, Sudhin, Sadasivan, Durgadevi, Ravindran, Roshni, Prithiviraj Swasthikka, Kumar, Ponnuchamy, Veera Ravi, Arumugam
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container_title International journal of biological macromolecules
container_volume 226
creator Abirami, Gurusamy
Alexpandi, Rajaiah
Sudhin, Sadasivan
Durgadevi, Ravindran
Roshni, Prithiviraj Swasthikka
Kumar, Ponnuchamy
Veera Ravi, Arumugam
description Acinetobacter baumannii, a virulent uropathogen with widespread antibiotic resistance, has arisen as a critical scientific challenge, necessitating the development of innovative therapeutic agents. This is the first study reveal the proteomic changes in A. baumannii upon pyrogallol treatment for understanding the mechanisms using nano-LC-MS/MS-based quantitative proteomics and qPCR analysis. The obtained results found that pyrogallol treatment dramatically downregulated the expression level of several key proteins such as GroEL, DnaK, ClpB, SodB, KatE, Bap, CsuA/B, PgaA, PgaC, BfmR, OmpA, and SecA in A. baumannii, which are involved in chaperone-mediated oxidative stress responses, antioxidant defence system, biofilm formation, virulence enzyme production, bacterial adhesion, capsule formation, and antibiotic resistance. Accordingly, the pyrogallol dramatically enhanced the lifespan of A. baumannii-infected zebrafish by inhibiting bacterial colonization, demonstrating the anti-infective potential of pyrogallol against A. baumannii. Further, the histopathological results also demonstrated the disease protection efficacy of pyrogallol against the pathognomonic sign of A. baumannii infection. In addition, the pyrogallol treatment effectively improved the immune parameters such as serum myeloperoxidase activity, leukocyte respiratory burst activity, and serum lysozyme activity in zebrafish against A. baumannii infection. Based on the results, the present study strongly proposes pyrogallol as a promising therapeutic agent for treating A. baumannii infection. •First study on proteomic changes in A. baumannii upon pyrogallol treatment.•Pyrogallol downregulated the expression level of several key proteins in A. baumannii.•Proteomic results were further validated by qPCR analysis and bioassays.•First study on anti-infective potential of pyrogallol against A. baumannii in zebrafish model.•Pyrogallol treatment improved the immune parameters in zebrafish.
doi_str_mv 10.1016/j.ijbiomac.2022.12.045
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subjects Acinetobacter baumannii - metabolism
Animals
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Anti-infective activity
Anti-Infective Agents - metabolism
Antivirulence activity
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biofilms
Immunity
Proteomics
Pyrogallol - metabolism
Pyrogallol - pharmacology
Quantitative proteomics
Tandem Mass Spectrometry
Virulence
Zebrafish - metabolism
title Pyrogallol downregulates the expression of virulence-associated proteins in Acinetobacter baumannii and showing anti-infection activity by improving non-specific immune response in zebrafish model
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