Dual-species proteomics and targeted intervention of animal-pathogen interactions.

Liu, Yang Sylvia; Zhang, Chengqian; Khoo, Bee Luan; Hao, Piliang; Chua, Song Lin

Liu, Yang Sylvia; Zhang, Chengqian; Khoo, Bee Luan; Hao, Piliang; Chua, Song Lin.

Afiliación

Liu YS; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region.
Zhang C; School of Life Science and Technology, ShanghaiTech University, China.
Khoo BL; Department of Biomedical Engineering, City University of Hong Kong, Hong Kong Special Administrative Region; Hong Kong Center for Cerebro-Cardiovascular Health Engineering (COCHE), Hong Kong Special Administrative Region; City University of Hong Kong-Shenzhen Futian Research Institute, Shenzhen, Chi
Hao P; School of Life Science and Technology, ShanghaiTech University, China. Electronic address: haopl@shanghaitech.edu.cn.
Chua SL; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region; State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region; Research

J Adv Res ; 2024 Sep 02.

Article en En | MEDLINE | ID: mdl-39233003

ABSTRACT

ABSTRACT

INTRODUCTION:

Host-microbe interactions are important to human health and ecosystems globally, so elucidating the complex host-microbe interactions and associated protein expressions drives the need to develop sensitive and accurate biochemical techniques. Current proteomics techniques reveal information from the point of view of either the host or microbe, but do not provide data on the corresponding partner. Moreover, it remains challenging to simultaneously study host-microbe proteomes that reflect the direct competition between host and microbe. This raises the need to develop a dual-species proteomics method for host-microbe interactions.

OBJECTIVES:

We aim to establish a forward + reverse Stable Isotope Labeling with Amino acids in Cell culture (SILAC) proteomics approach to simultaneously label and quantify newly-expressed proteins of host and microbe without physical isolation, for investigating mechanisms in direct host-microbe interactions.

METHODS:

Using Caenorhabditis elegans-Pseudomonas aeruginosa infection model as proof-of-concept, we employed SILAC proteomics and molecular pathway analysis to characterize the differentially-expressed microbial and host proteins. We then used molecular docking and chemical characterization to identify chemical inhibitors that intercept host-microbe interactions and eliminate microbial infection.

RESULTS:

Based on our proteomics results, we studied the iron competition between pathogen iron scavenger and host iron uptake protein, where P. aeruginosa upregulated pyoverdine synthesis protein (PvdA) (fold-change of 5.2313) and secreted pyoverdine, and C. elegans expressed ferritin (FTN-2) (fold-change of 3.4057). Targeted intervention of iron competition was achieved using Galangin, a ginger-derived phytochemical that inhibited pyoverdine production and biofilm formation in P. aeruginosa. The Galangin-ciprofloxacin combinatorial therapy could eliminate P. aeruginosa biofilms in a fish wound infection model, and enabled animal survival.

CONCLUSION:

Our work provides a novel SILAC-based proteomics method that can simultaneously evaluate host and microbe proteomes, with future applications in higher host organisms and other microbial species. It also provides insights into the mechanisms dictating host-microbe interactions, offering novel strategies for anti-infective therapy.

Palabras clave

Caenorhabditis elegans; Host-microbe interactions; Iron competition; Pseudomonas aeruginosa; SILAC proteomics

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Adv Res Año: 2024 Tipo del documento: Article Pais de publicación: Egipto