Gen-Yang Xin, Daxi Wang, Xin Zhang, Qingquan Cen, Minwu Peng, Yuqi Liao, Jing Wang, Shi-Jia Le, Jinxia Cheng, Wei-Chen Wu, Xin Hou, Gengyan Luo, Qinyu Gou, Jianbin Kong, Zhu Pan, Dongqing Li, Shipei Gan, An Chen, Hailong Zhao, Peibo Shi, Z. Y. Ren, Weiqi Zhao, Jiajun Liu, Penghui Jia, Changyun Sun, Wenqing Lin, Jun Wu, Guopeng Kuang, Jingdiao Chen, Junhua Li, Edward C. Holmes, Ziqing Deng, Mǎng Shī
Small mammals harbor a diverse array of potentially zoonotic pathogens. To date, however, metagenomic surveys of these species have primarily focused on viruses, with limited attention directed to bacterial and eukaryotic pathogens. Additionally, the ecological determinants of pathogen diversity within these mammals have not been systematically examined. Herein, we employed a metatranscriptomics approach to survey the pathogen infectome—defined as the set of microorganisms infecting the host—across 2408 individual samples, representing lung, spleen, and gut from 858 animals in Guangdong province, China, considering the impact of host species, tissue, season, and geographic location on pathogen diversity. We identified 76 potential pathogen species, comprising 29 RNA viruses, 12 DNA viruses, five bacteria, and 30 eukaryotic pathogens, including 33 that are newly discovered. Distinct tissue tropisms were identified, suggesting varied transmission routes. Individual animals carried an average of one pathogen, with 10 pathogens widely distributed among mammalian orders. Total pathogen richness was largely influenced by geographic region, followed by host species and season, while zoonotic pathogen richness was primarily driven by host species. Collectively, these data provide insights into the structure of the pathogen infectome and the drivers of pathogen diversity and transmission in these key mammalian disease reservoirs. Less is known about the entire microbial pathogen profile of small mammals. Here, the authors analyse 2,408 tissue-resolved metatranscriptomes to map the infectome in small mammals, uncovering high viral, bacterial, fungal and parasitic diversity and showing how geography, hosts, and seasons shape zoonotic risk.