Pseudomonas aeruginosa biofilm dispersion by the mouse antimicrobial peptide CRAMP

Author:

Zhang Yang,Cheng Peng,Wang Shiyuan,Li Xiaofen,Peng Lianci,Fang Rendong,Xiong Jing,Li Hui,Mei Cui,Gao Jiye,Song Zhenhui,Xu Dengfeng,Fu Lizhi,Li Chenghong,Wu Xueqing,He Yuzhang,Chen HongweiORCID

Abstract

AbstractPseudomonas aeruginosa (P. aeruginosa) is a known bacterium that produces biofilms and causes severe infection. Furthermore, P. aeruginosa biofilms are extremely difficult to eradicate, leading to the development of chronic and antibiotic-resistant infections. Our previous study showed that a cathelicidin-related antimicrobial peptide (CRAMP) inhibits the formation of P. aeruginosa biofilms and markedly reduces the biomass of preformed biofilms, while the mechanism of eradicating bacterial biofilms remains elusive. Therefore, in this study, the potential mechanism by which CRAMP eradicates P. aeruginosa biofilms was investigated through an integrative analysis of transcriptomic, proteomic, and metabolomic data. The omics data revealed CRAMP functioned against P. aeruginosa biofilms by different pathways, including the Pseudomonas quinolone signal (PQS) system, cyclic dimeric guanosine monophosphate (c-di-GMP) signalling pathway, and synthesis pathways of exopolysaccharides and rhamnolipid. Moreover, a total of 2914 differential transcripts, 785 differential proteins, and 280 differential metabolites were identified. A series of phenotypic validation tests demonstrated that CRAMP reduced the c-di-GMP level with a decrease in exopolysaccharides, especially alginate, in P. aeruginosa PAO1 biofilm cells, improved bacterial flagellar motility, and increased the rhamnolipid content, contributing to the dispersion of biofilms. Our study provides new insight into the development of CRAMP as a potentially effective antibiofilm dispersant.

Funder

Graduate Research and Innovation Projects of Chongqing

Fundamental Research Funds for the Central Universities

Chongqing basic research and frontier exploration project

Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project

National Outstanding Youth Science Fund Project of National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

General Veterinary

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