An expanded database and analytical toolkit for identifying bacterial virulence factors and their associations with chronic diseases

Wanting Dong, Xinyue Fan, Yaqiong Guo, Siyi Wang, Shulei Jia, Na Lv, Tao Yuan, Yuanlong Pan, Yong Xue, Xi Chen, Qian Xiong, Ruifu Yang (), Weigang Zhao () and Baoli Zhu ()
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Wanting Dong: Chinese Academy of Sciences
Xinyue Fan: Chinese Academy of Sciences
Yaqiong Guo: Beijing Academy of Science and Technology
Siyi Wang: Chinese Academy of Sciences
Shulei Jia: Tianjin Medical University
Na Lv: Chinese Academy of Sciences
Tao Yuan: Chinese Academy of Medical Science and Peking Union Medical College
Yuanlong Pan: Chinese Academy of Sciences
Yong Xue: China Agricultural University
Xi Chen: Nanjing Agricultural University
Qian Xiong: Chinese Academy of Sciences
Ruifu Yang: Beijing Institute of Microbiology and Epidemiology
Weigang Zhao: Chinese Academy of Medical Science and Peking Union Medical College
Baoli Zhu: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Virulence factor genes (VFGs) play pivotal roles in bacterial infections and have been identified within the human gut microbiota. However, their involvement in chronic diseases remains poorly understood. Here, we establish an expanded VFG database (VFDB 2.0) consisting of 62,332 nonredundant orthologues and alleles of VFGs using species-specific average nucleotide identity ( https://github.com/Wanting-Dong/MetaVF_toolkit/tree/main/databases ). We further develop the MetaVF toolkit, facilitating the precise identification of pathobiont-carried VFGs at the species level. A thorough characterization of VFGs for 5452 commensal isolates from healthy individuals reveals that only 11 of 301 species harbour these factors. Further analyses of VFGs within the gut microbiomes of nine chronic diseases reveal both common and disease-specific VFG features. Notably, in type 2 diabetes patients, long HiFi sequencing confirms that shared VF features are carried by pathobiont strains of Escherichia coli and Klebsiella pneumoniae. These findings underscore the critical importance of identifying and understanding VFGs in microbiome-associated diseases.

Date: 2024
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DOI: 10.1038/s41467-024-51864-y

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