AUTHOR=Garomsa Tadesse Lejisa , Shenkutie Abebe Mekuria , Leung Polly H. M. TITLE=Recent advances in host models in studying virulence factors and pathogenesis of Acinetobacter baumannii JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1715193 DOI=10.3389/fcimb.2025.1715193 ISSN=2235-2988 ABSTRACT=Acinetobacter baumannii is a major global healthcare-associated pathogen with increased antibiotic resistance, underscoring the urgent need to develop novel antibiotics, immunotherapies, and vaccines. However, a critical gap in combating A. baumannii infections is the lack of a systematic approach to selecting appropriate host models for studying host-pathogen interactions. This review analyses previously published research articles on host interactions with A. baumannii. The articles were searched from electronic databases, including PubMed, ScienceDirect, and Google Scholar, covering publications from 2015 to 2024. These studies, encompassing both in vitro and in vivo research, aim to elucidate the virulence factors and host responses during host-pathogen interactions. The review analysis shows that mouse and Galleria mellonella are well-established animal models. Meanwhile, A549, HEK-293, HeLa, and Hep-G2 cell lines are the main in vitro models for studying A. baumannii pathogenesis. Key considerations for in vitro host model selection include necessitating a minimum of biosafety level 2 (BSL-2) laboratory conditions, the specific pathogens involved, relevance of the cell lines, immune responsiveness, and ease of manipulation. Challenges such as the heterogeneity of bacterial strains, initial bacterial dose, incubation duration, and infection multiplicity should be considered in host-pathogen studies. This review could serve as a roadmap for optimizing experimental models to accelerate the development of targeted strategies against A. baumannii.