한빛사논문
중앙대학교
Baolei Jia 1 2 * †, Ju Hye Baek 2 †, Jae Kyeong Lee 2 †, Ying Sun 3, Kyung Hyun Kim 4, Ji Young Jung 5, Che Ok Jeon 2 *
1Xianghu Laboratory, Hangzhou, 311231, China.
2Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
3Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, 1870, Denmark.
4Department of Biological Sciences and Biotechnology, Hannam University, Daejon, 34054, Republic of Korea.
5Microbial Research Department, Nakdonggang National Institute of Biological Resources, Gyeongsangbuk-do, 37242, Republic of Korea.
†B.J., J.H.B., and J.K.L. contributed equally to this work
*Corresponding author: correspondence to Baolei Jia or Che Ok Jeon
Abstract
β-lactams, the most common antibiotics globally, have resistance primarily determined by β-lactamases. Human microbiota and β-lactams influence mutually; however, β-lactamase variety and abundance in the human microbiome remain partially understood. This study aimed to elucidate the diversity, abundance, and substrate spectrum of β-lactamases. 1369 characterized β-lactamases and 16 204 putative sequences are collected from protein databases. Upon clustering analysis and biochemical assays, nine proteins exhibiting less than 35% identity to those previously characterized are confirmed as β-lactamases. These newly identified β-lactamases originated from eight distinct clusters comprising 1163 β-lactamases. Quantifying healthy participants (n = 2394) across 19 countries using functionally confirmed clusters revealed that Japan have the highest gut β-lactamase abundance (log2[reads per million (RPM)] = 6.52) and Fiji have the lowest (log2[RPM] = 2.31). The β-lactamase abundance is correlated with β-lactam consumption (R = 0.50, p = 0.029) and income (R = 0.51, p = 0.024). Comparing individuals with ailments with healthy participants, β-lactamase abundance in the gut is increased significantly in patients with colorectal cancer, cardiovascular diseases, breast cancer, and epilepsy. These outcomes provide insights into investigating antibiotic resistance, antibiotic stewardship, and gut microbiome-antibiotic interactions.
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