title: Functional screening of antibiotic resistance genes from human gut microbiota reveals a novel gene fusion.
abstract: The human gut microbiota has a high density of bacteria that are considered a reservoir for antibiotic resistance genes (ARGs). In this study, one fosmid metagenomic library generated from the gut microbiota of four healthy humans was used to screen for ARGs against seven antibiotics. Eight new ARGs were obtained: one against amoxicillin, six against d-cycloserine, and one against kanamycin. The new amoxicillin resistance gene encodes a protein with 53% identity to a class D β-lactamase from Riemerella anatipestifer RA-GD. The six new d-cycloserine resistance genes encode proteins with 73-81% identity to known d-alanine-d-alanine ligases. The new kanamycin resistance gene encodes a protein of 274 amino acids with an N-terminus (amino acids 1-189) that has 42% identity to the 6'-aminoglycoside acetyltransferase [AAC(6')] from Enterococcus hirae and a C-terminus (amino acids 190-274) with 35% identity to a hypothetical protein from Clostridiales sp. SSC/2. A functional study on the novel kanamycin resistance gene showed that only the N-terminus conferred kanamycin resistance. Our results showed that functional metagenomics is a useful tool for the identification of new ARGs.
authors: Microbial Genome Research Center, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors: Gong
authors: G
authors: Cheng
authors: Yongfei
authors: Y
authors: Hu
authors: Yeshi
authors: Y
authors: Yin
authors: Xi
authors: X
authors: Yang
authors: Chunsheng
authors: C
authors: Xiang
authors: Baohong
authors: B
authors: Wang
authors: Yanfei
authors: Y
authors: Chen
authors: Fengling
authors: F
authors: Yang
authors: Fang
authors: F
authors: Lei
authors: Na
authors: N
authors: Wu
authors: Na
authors: N
authors: Lu
authors: Jing
authors: J
authors: Li
authors: Quanze
authors: Q
authors: Chen
authors: Lanjuan
authors: L
authors: Li
authors: Baoli
authors: B
authors: Zhu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D041981:Gastrointestinal Tract / Q000382:microbiology*; D050939:Gene Fusion; D006801:Humans; D054892:Metagenome; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010802:Phylogeny
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins