Abstract
Fish are a potential source of diverse organic compounds with a broad spectrum of biological activities. Many fish-derived antimicrobial peptides and proteins are key components of the fish innate immune system. They are also potential candidates for development of new antimicrobial agents. CXCL20b is a grass carp (Ctenopharyngodon idella) CXC chemokine strongly transcribed at the early stage of bacterial infections, for which the immune role had not been reported to date. In the present study, we found that CXCL20b is a cationic amphipathic protein that displays potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. The results of DiOC2(3) and atomic force microscopy (AFM) assays indicated that CXCL20b could induce bacterial membrane depolarization and disruption in a short time. By performing further structure-activity studies, we found that the antimicrobial activity of CXCL20b was mainly relative to the N-terminal random coil region. The central part of this cytokine representing β-sheet region was insoluble in water and the C-terminal α-helical region did not show an antimicrobial effect. The results presented in this article support the poorly understood function of CXCL20b, which fulfills an important role in bony fish antimicrobial immunity.
Highlights
The innate immune system, largely based on antimicrobial peptides (AMPs) [1], provides a front line of defense against invading bacterial pathogen
Atomic force microscopy (AFM) assays indicated that CXCL20b could induce bacterial membrane depolarization and disruption in a short time
We showed that CXCL20b could efficiently kill bacteria by causing bacterial membrane depolarization and disruption
Summary
The innate immune system, largely based on antimicrobial peptides (AMPs) [1], provides a front line of defense against invading bacterial pathogen. There are over one hundred human AMPs have been reported [2]. The major members include cathelicidins [3], defensins [4], histatins [5], RNases [6], dermcidin [7], and antimicrobial chemokines [8]. AMPscan selectively permeate bacterial membranes and kill via disruption of the barrier function. The increasing incidence of infections resulting from multiple drug-resistant pathogens in clinical settings has intensified the demand for alternative therapies. AMPs with potent antimicrobial activities and diverse mechanisms of action are considered important alternatives to solving the issues of multiple drug-resistance [10]
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