| Autor: |
Xue Li Guan, Johnathan Yi-Xiong Loh, Marco Lizwan, Sharon Cui Mun Chan, Jeric Mun Chung Kwan, Tze Peng Lim, Tse Hsien Koh, Li-Yang Hsu, Bernett Teck Kwong Lee |
| Přispěvatelé: |
Lee Kong Chian School of Medicine (LKCMedicine), Immunology Network (SIgN), A*STAR, Centre for Biomedical Informatics |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Analytical chemistry. |
| ISSN: |
1520-6882 |
| Popis: |
With the global emergence of drug-resistant bacteria causing difficult-to-treat infections, there is an urgent need for a tool to facilitate studies on key virulence and antimicrobial resistant factors. Mass spectrometry (MS) has contributed substantially to the elucidation of the structure-function relationships of lipid A, the endotoxic component of lipopolysaccharide which also serves as an important protective barrier against antimicrobials. Here, we present LipidA-IDER, an automated structure annotation tool for system-level scale identification of lipid A from high-resolution tandem mass spectrometry (MS2) data. LipidA-IDER was validated against previously reported structures of lipid A in the reference bacteria, Escherichia coli and Pseudomonas aeruginosa. Using MS2 data of variable quality, we demonstrated LipidA-IDER annotated lipid A with a performance of 71.2% specificity and 70.9% sensitivity, offering greater accuracy than existing lipidomics software. The organism-independent workflow was further applied to a panel of six bacterial species: E. coli and Gram-negative members of ESKAPE pathogens. A comprehensive atlas comprising 188 distinct lipid A species, including remodeling intermediates, was generated and can be integrated with software including MS-DIAL and Metabokit for identification and semiquantitation. Systematic comparison of a pair of polymyxin-sensitive and polymyxin-resistant Acinetobacter baumannii isolated from a human patient unraveled multiple key lipid A structural features of polymyxin resistance within a single analysis. Probing the lipid A landscape of bacteria using LipidA-IDER thus holds immense potential for advancing our understanding of the vast diversity and structural complexity of a key lipid virulence and antimicrobial-resistant factor. LipidA-IDER is freely available at https://github.com/Systems-Biology-Of-Lipid-Metabolism-Lab/LipidA-IDER. Ministry of Education (MOE) Nanyang Technological University This work was supported by the Nanyang Assistant Professorship from Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), and the Ministry of Education (MOE) Tier 2 grant (MOE2017-T2-1-042), awarded to X.L.G. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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