Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression
ABSTRACT Acinetobacter baumannii commonly causes lower airway colonization and infection and is easily confused. This study aimed to analyze the biological characteristics of carbapenem-resistant A. baumannii (CRAB) ST2 in the lower airway and identify an effective method for distinguishing between...
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American Society for Microbiology
2025-06-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00195-25 |
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| author | DingYun Feng JianXia Zhou Logen Liu Ying Li RongHua Zhong WenBin Wu WenZheng Zheng TianTuo Zhang |
| author_facet | DingYun Feng JianXia Zhou Logen Liu Ying Li RongHua Zhong WenBin Wu WenZheng Zheng TianTuo Zhang |
| author_sort | DingYun Feng |
| collection | DOAJ |
| description | ABSTRACT Acinetobacter baumannii commonly causes lower airway colonization and infection and is easily confused. This study aimed to analyze the biological characteristics of carbapenem-resistant A. baumannii (CRAB) ST2 in the lower airway and identify an effective method for distinguishing between A. baumannii colonization and infection. Lower airway CRAB ST2 isolated at the Department of Respiratory and Critical Care Medicine and intensive care unit of our hospital from January 2021 to June 2023 were included, and their whole genome, biofilm-forming ability, bacterial virulence, and metabolome were analyzed. Fifty-six strains of CRAB with ST2 were identified, of which 32 were infection strains and 24 were colonization strains. The virulence and resistance genes, as well as the virulence and biofilm-forming ability, of ST2-type carbapenem-resistant lower airway infecting and colonizing A. baumannii strains were similar. The levels of metabolites were significantly lower in ST2-type carbapenem-resistant lower airway-infecting A. baumannii infection strains than those in the lower airway-colonizing strains. The levels of (S)-(+)−2-(aniline methyl) pyrrolidine, valine, ketoleucine, L-isoleucine, homoserine, N-acetyl-L-aspartate, and 2-aminoethanol-1-phosphate in the lower airway infection strains were significantly lower than those in the lower airway colonization strains. Bacterial virulence tests and biofilm formation ability could not distinguish the same ST of CRAB in the lower airway from the colonization or infection strains; however, metabolomics could. The biosynthesis and degradation pathways of valine, leucine, and isoleucine were downregulated, and changes in their metabolism may be important factors in promoting carbapenem-resistant A. baumanniiCRAB transformation from colonization to infection.IMPORTANCECarbapenem-resistant A. baumannii (CRAB) poses a critical threat in clinical settings, particularly due to challenges in distinguishing airway colonization from active infection, which complicates treatment decisions. This study highlights the limitations of conventional approaches—such as virulence gene profiling, phenotypic virulence assays, and biofilm formation analysis—in differentiating CRAB ST2 strains isolated from lower airway infections versus colonization. By integrating metabolomics, we identified distinct metabolic signatures linked to infection, including significant downregulation of valine, leucine, and isoleucine biosynthesis/degradation pathways and reduced levels of key metabolites (e.g., ketoleucine and L-isoleucine) in infection strains. These findings provide the first evidence that metabolic dysregulation may drive CRAB’s transition from colonization to invasive disease. This work advances our understanding of CRAB pathogenicity and offers a novel, metabolism-based strategy to improve diagnostic accuracy, guide targeted therapies, and optimize antimicrobial stewardship in managing CRAB-associated respiratory infections. |
| format | Article |
| id | doaj-art-858e89de26cd4c33977cd22bc9e73a3b |
| institution | DOAJ |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj-art-858e89de26cd4c33977cd22bc9e73a3b2025-08-20T03:19:25ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-06-0113610.1128/spectrum.00195-25Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progressionDingYun Feng0JianXia Zhou1Logen Liu2Ying Li3RongHua Zhong4WenBin Wu5WenZheng Zheng6TianTuo Zhang7Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases of Sun Yat-Sen University, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases of Sun Yat-Sen University, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaClinical Research Center, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, ChinaNational Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Academy of Sciences, Institute of Microbiology, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases of Sun Yat-Sen University, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases of Sun Yat-Sen University, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases of Sun Yat-Sen University, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases of Sun Yat-Sen University, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaABSTRACT Acinetobacter baumannii commonly causes lower airway colonization and infection and is easily confused. This study aimed to analyze the biological characteristics of carbapenem-resistant A. baumannii (CRAB) ST2 in the lower airway and identify an effective method for distinguishing between A. baumannii colonization and infection. Lower airway CRAB ST2 isolated at the Department of Respiratory and Critical Care Medicine and intensive care unit of our hospital from January 2021 to June 2023 were included, and their whole genome, biofilm-forming ability, bacterial virulence, and metabolome were analyzed. Fifty-six strains of CRAB with ST2 were identified, of which 32 were infection strains and 24 were colonization strains. The virulence and resistance genes, as well as the virulence and biofilm-forming ability, of ST2-type carbapenem-resistant lower airway infecting and colonizing A. baumannii strains were similar. The levels of metabolites were significantly lower in ST2-type carbapenem-resistant lower airway-infecting A. baumannii infection strains than those in the lower airway-colonizing strains. The levels of (S)-(+)−2-(aniline methyl) pyrrolidine, valine, ketoleucine, L-isoleucine, homoserine, N-acetyl-L-aspartate, and 2-aminoethanol-1-phosphate in the lower airway infection strains were significantly lower than those in the lower airway colonization strains. Bacterial virulence tests and biofilm formation ability could not distinguish the same ST of CRAB in the lower airway from the colonization or infection strains; however, metabolomics could. The biosynthesis and degradation pathways of valine, leucine, and isoleucine were downregulated, and changes in their metabolism may be important factors in promoting carbapenem-resistant A. baumanniiCRAB transformation from colonization to infection.IMPORTANCECarbapenem-resistant A. baumannii (CRAB) poses a critical threat in clinical settings, particularly due to challenges in distinguishing airway colonization from active infection, which complicates treatment decisions. This study highlights the limitations of conventional approaches—such as virulence gene profiling, phenotypic virulence assays, and biofilm formation analysis—in differentiating CRAB ST2 strains isolated from lower airway infections versus colonization. By integrating metabolomics, we identified distinct metabolic signatures linked to infection, including significant downregulation of valine, leucine, and isoleucine biosynthesis/degradation pathways and reduced levels of key metabolites (e.g., ketoleucine and L-isoleucine) in infection strains. These findings provide the first evidence that metabolic dysregulation may drive CRAB’s transition from colonization to invasive disease. This work advances our understanding of CRAB pathogenicity and offers a novel, metabolism-based strategy to improve diagnostic accuracy, guide targeted therapies, and optimize antimicrobial stewardship in managing CRAB-associated respiratory infections.https://journals.asm.org/doi/10.1128/spectrum.00195-25metabolomicsAcinetobacter baumanniicolonizationinfection |
| spellingShingle | DingYun Feng JianXia Zhou Logen Liu Ying Li RongHua Zhong WenBin Wu WenZheng Zheng TianTuo Zhang Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression Microbiology Spectrum metabolomics Acinetobacter baumannii colonization infection |
| title | Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression |
| title_full | Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression |
| title_fullStr | Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression |
| title_full_unstemmed | Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression |
| title_short | Integrated multi-omics reveals metabolic determinants of CRAB ST2 airway infection progression |
| title_sort | integrated multi omics reveals metabolic determinants of crab st2 airway infection progression |
| topic | metabolomics Acinetobacter baumannii colonization infection |
| url | https://journals.asm.org/doi/10.1128/spectrum.00195-25 |
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