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

Abstract

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.

Keywords: Anti-infective activity; Antivirulence activity; Quantitative proteomics.