Caerin 1.1/1.9 peptides control Acinetobacter baumannii infection through combined antibacterial and host-directed immunomodulatory mechanisms

Hongyin Wu; Junjie Li; Jinyi Wu; Quanlan Fu; Yuandong Luo; Yongxin Liang; Furong Zhong; Bin Xu; Zhijun Lin; Tianfang Wang; Xiaosong Liu; Guoying Ni

doi:10.3389/fmicb.2026.1777814

Back

Caerin 1.1/1.9 peptides control Acinetobacter baumannii infection through combined antibacterial and host-directed immunomodulatory mechanisms

Journal article

Open access

Peer reviewed

Caerin 1.1/1.9 peptides control Acinetobacter baumannii infection through combined antibacterial and host-directed immunomodulatory mechanisms

Hongyin Wu, Junjie Li, Jinyi Wu, Quanlan Fu, Yuandong Luo, Yongxin Liang, Furong Zhong, Bin Xu, Zhijun Lin, Tianfang Wang, …

Frontiers in Microbiology, Vol.17, pp.1-14

2026

DOI: https://doi.org/10.3389/fmicb.2026.1777814

Files and links (1)

pdf

fmicb-17-17778143.22 MBDownload View

Published Version Open Access CC BY V4.0

Abstract

Acinetobacter baumannii

antimicrobial peptides

immune regulation

immunomodulation

macrophage polarization

Introduction: Acinetobacter baumannii is a major multidrug-resistant (MDR) pathogen associated with high morbidity and mortality, driven not only by antibiotic resistance but also by its ability to persist intracellularly and disrupt host immune homeostasis. Host-directed antimicrobial strategies that combine bactericidal activity with immune modulation are therefore urgently needed. Caerin peptides 1.1 (F1) and 1.9 (F3), derived from Australian tree frogs, have demonstrated broad antimicrobial activity, but their combined antibacterial and immunomodulatory mechanisms remain incompletely understood.Methods: We evaluated the antimicrobial and host-directed effects of F1/F3 using in vitro A549 epithelial infection models and an in vivo murine skin-injury infection model. Antibacterial activity was assessed by minimum inhibitory concentration (MIC) assays and colony-forming unit (CFU) quantification. Host cell responses were analyzed using viability, LDH release, reactive oxygen species (ROS), and apoptosis assays. Immune modulation in vivo was investigated by flow cytometry, multiplex immunofluorescence, and cytokine profiling.Results: F1/F3 exhibited potent antibacterial activity against A. baumannii (MIC 3.75 μg/mL) with minimal cytotoxicity to host cells. The peptides significantly reduced intracellular bacterial burden while alleviating infection-induced oxidative stress and early apoptosis. In vivo, F1/F3 treatment reduced bacterial colonization, improved tissue integrity, and reshaped the immune microenvironment. This included increased macrophage infiltration with a shift toward a reparative phenotype, reduced neutrophil accumulation, enhanced dendritic cell presence, and coordinated upregulation of pro- and anti-inflammatory cytokines, including IL-6, IL-12, IFN-γ, IL-10, and TGF-β, without altering TNF-α levels.Discussion: These findings demonstrate that F1/F3 exert a dual mode of action by combining direct antibacterial effects with host-directed immunomodulation. By integrating microbial suppression, immune reprogramming, and tissue repair, caerin peptides represent promising candidates for the development of next-generation therapies against MDR A. baumannii infections.

Details

Title: Caerin 1.1/1.9 peptides control Acinetobacter baumannii infection through combined antibacterial and host-directed immunomodulatory mechanisms
Authors: Hongyin Wu - First Affiliated Hospital of Guangdong Pharmaceutical University
Junjie Li - Zhongao Biomedical Technology (China)
Jinyi Wu - First Affiliated Hospital of Guangdong Pharmaceutical University
Quanlan Fu - Zhongao Biomedical Technology (China)
Yuandong Luo - Zhongao Biomedical Technology (China)
Yongxin Liang - Zhongao Biomedical Technology (China)
Furong Zhong - First Affiliated Hospital of Guangdong Pharmaceutical University
Bin Xu - First Affiliated Hospital of Guangdong Pharmaceutical University
Zhijun Lin - Guizhou University
Tianfang Wang - University of the Sunshine Coast
Xiaosong Liu (Corresponding Author) - First Affiliated Hospital of Guangdong Pharmaceutical University
Guoying Ni (Corresponding Author) - University of the Sunshine Coast
Publication details: Frontiers in Microbiology, Vol.17, pp.1-14
Publisher: Frontiers Research Foundation
Date published: 2026
DOI: 10.3389/fmicb.2026.1777814
ISSN: 1664-302X
Copyright note: © 2026 Wu, Li, Wu, Fu, Luo, Liang, Zhong, Xu, Lin, Wang, Liu and Ni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Data Availability: The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.
Grant note: This study was supported in part by the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Science and Technology Department (2016A020213001), the National Science Foundation of Guangdong province (2020A1515010855), the National Science Foundation of China (31971355), and The Deng Feng Project of First People’s Hospital of Foshan (2019A008).
Organisation Unit: School of Science and Engineering - Legacy; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering
Language: English
Record Identifier: 991231326102621
Output Type: Journal article

Metrics

1 Record Views