The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes.
Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants. However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown. Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (≥99% nucleotide identity) of mobile ARGs. We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites. Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiomes are also harbored by diverse human pathogens. Taking these results together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens.



The development of antibiotic resistance threatens our modern medical achievements. The dissemination of antibiotic resistance can be largely attributed to the transfer of bacterial mobile antibiotic resistance genes (ARGs). Revealing the transfer network of these genes in bacteria and the forces driving the gene flow is of great importance for controlling and predicting the emergence of antibiotic resistance in the clinic. Here, by analyzing tens of thousands of bacterial genomes and millions of human and animal gut bacterial genes, we reveal that the transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under ecological constraints. We also found that dozens of ARGs are transferred between the human and animal gut and human pathogens. This work demonstrates the whole profile of mobile ARGs and their transfer network in bacteria and provides further insight into the evolution and spread of antibiotic resistance in nature.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Yongfei
Y
Hu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Xi
X
Yang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China.
Jing
J
Li
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China.
Na
N
Lv
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Fei
F
Liu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China.
Jun
J
Wu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China.
Ivan Y C
IY
Lin
Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
Na
N
Wu
Department of Population Health and Reproduction, 100K Pathogen Genome Project, School of Veterinary Medicine, University of California, Davis, California, USA.
Bart C
0000-0002-7471-1978
BC
Weimer
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Office of Director-General, Chinese Center for Disease Control and Prevention, Beijing, China.
George F
GF
Gao
Department of Gastroenterology, Peking University People's Hospital, Beijing, China zhubaoli@im.ac.cn liuyulan@pkuph.edu.cn.
Yulan
Y
Liu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Beijing Key Laboratory of Microbial Drug Resistance and Resistome, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China zhubaoli@im.ac.cn liuyulan@pkuph.edu.cn.
Baoli
B
Zhu
D000818:Animals; D000829:Animals, Domestic / Q000382:microbiology; D001419:Bacteria / Q000235:genetics / Q000472:pathogenicity; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017753:Ecosystem; D041981:Gastrointestinal Tract / Q000382:microbiology; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D006801:Humans; D054892:Metagenome; D064307:Microbiota / Q000235:genetics*; D010802:Phylogeny; D020560:Proteobacteria / Q000235:genetics; D012336:RNA, Ribosomal, 16S; D012988:Soil Microbiology
D012336:RNA, Ribosomal, 16S