Proteomics Landscape of Host-Pathogen Interaction in Acinetobacter baumannii Infected Mouse Lung
Xin Li1,2,3, Xiaofen Liu1,2,3, Peter Horvatovich4
1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Abstract:
Acinetobacter baumannii is an important pathogen of nosocomial infection worldwide, which can primarily cause pneumonia, bloodstream infection, and urinary tract infection. The increasing drug resistance rate of A. baumannii and the slow development of new antibacterial drugs brought great challenges for clinical treatment. Host immunity is crucial to the defense of A. baumannii infection, and understanding the mechanisms of immune response can facilitate the development of new therapeutic strategies. To characterize the system-level changes of host proteome in immune response, we used tandem mass tag (TMT) labeling quantitative proteomics to compare the proteome changes of lungs from A. baumannii infected mice with control mice 6 h after infection. A total of 6,218 proteins were identified in which 6,172 could be quantified. With threshold p < 0.05 and relative expression fold change > 1.2 or < 0.83, we found 120 differentially expressed proteins. Bioinformatics analysis showed that differentially expressed proteins after infection were associated with receptor recognition, NADPH oxidase (NOX) activation and antimicrobial peptides. These differentially expressed proteins were involved in the pathways including leukocyte transendothelial migration, phagocyte, neutrophil degranulation, and antimicrobial peptides. In conclusion, our study showed proteome changes in mouse lung tissue due to A. baumannii infection and suggested the important roles of NOX, neutrophils, and antimicrobial peptides in host response. Our results provide a potential list of protein candidates for the further study of host-bacteria interaction in A. baumannii infection. Data are available via ProteomeXchange with identifier PXD020640.
Insights
This study reveals key host proteome changes in mouse lungs during Acinetobacter baumannii infection. It highlights the roles of NADPH oxidase, neutrophils, and antimicrobial peptides in fighting this dangerous nosocomial pathogen.
Area of Science:
- Microbiology
- Immunology
- Proteomics
Background:
- Acinetobacter baumannii is a major cause of hospital-acquired infections worldwide, leading to pneumonia, bloodstream, and urinary tract infections.
- Rising antibiotic resistance in A. baumannii and a lack of new drug development pose significant clinical challenges.
- Understanding host immune responses is critical for developing novel therapeutic strategies against A. baumannii.
Purpose of the Study:
- To investigate system-level proteome alterations in the host lung during A. baumannii infection.
- To identify key proteins and pathways involved in the host immune response to A. baumannii.
Main Methods:
- Quantitative proteomics using tandem mass tag (TMT) labeling was employed.
- Lung proteomes of A. baumannii-infected mice were compared to control mice 6 hours post-infection.
- Bioinformatics analysis was used to identify differentially expressed proteins and associated pathways.
Main Results:
- A total of 6,218 proteins were identified, with 6,172 quantified.
- 120 differentially expressed proteins were identified (p < 0.05, fold change > 1.2 or < 0.83).
- Differentially expressed proteins were linked to receptor recognition, NADPH oxidase (NOX) activation, and antimicrobial peptides, involving pathways like leukocyte transendothelial migration and neutrophil degranulation.
Conclusions:
- The study characterized proteome changes in mouse lung tissue following A. baumannii infection.
- NADPH oxidase, neutrophils, and antimicrobial peptides play significant roles in the host's defense against A. baumannii.
- Identified proteins offer potential candidates for further research into host-pathogen interactions in A. baumannii infections.
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