14.
Enterotypes of the human gut mycobiome.
Lai S, Yan Y, Pu Y, Lin S, Qiu JG, Jiang BH, Keller MI, Wang M,
Bork P,
Chen WH, Zheng Y,
Zhao XM
Abstract + PDF
The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. However, the overall structure of the gut mycobiome as well as the inter-individual variations in fungal composition remains largely unknown. In this study, we collected a total of 3363 fungal sequencing samples from 16 cohorts across three continents, including 572 newly profiled samples from China.
13.
Computational exploration of the global microbiome for antibiotic discovery.
Santos-Júnior CD, Torres MDT, Duan Y, Rodríguez Del Río Á,
Schmidt TSB, Chong H,
Fullam A, Michael K, Zhu C, Houseman A, Somborski J, Vines A,
Zhao XM,
Bork P,
Huerta-Cepas J, de la Fuente-Nunez C,
Coelho LP2023 Sep 11; [Epub ahead of print] PubMed:
37693522.
Abstract
Novel antibiotics are urgently needed to combat the antibiotic-resistance crisis. We present a machine learning-based approach to predict prokaryotic antimicrobial peptides (AMPs) by leveraging a vast dataset of 63,410 metagenomes and 87,920 microbial genomes. This led to the creation of AMPSphere, a comprehensive catalog comprising 863,498 non-redundant peptides, the majority of which were previously unknown. We observed that AMP production varies by habitat, with animal-associated samples displaying the highest proportion of AMPs compared to other habitats. Furthermore, within different human-associated microbiota, strain-level differences were evident. To validate our predictions, we synthesized and experimentally tested 50 AMPs, demonstrating their efficacy against clinically relevant drug-resistant pathogens both in vitro and in vivo. These AMPs exhibited antibacterial activity by targeting the bacterial membrane. Additionally, AMPSphere provides valuable insights into the evolutionary origins of peptides. In conclusion, our approach identified AMP sequences within prokaryotic microbiomes, opening up new avenues for the discovery of antibiotics.
12.
Long-Read Sequencing Reveals Extensive DNA Methylations in Human Gut Phagenome Contributed by Prevalently Phage-Encoded Methyltransferases.
Sun C, Chen J, Jin M, Zhao X, Li Y, Dong Y, Gao N, Liu Z,
Bork P,
Zhao XM,
Chen WH2023 Sep 29; 10(25): e2302159. PubMed:
37382405.
Abstract + PDF
DNA methylation plays a crucial role in the survival of bacteriophages (phages), yet the understanding of their genome methylation remains limited. In this study, DNA methylation patterns are analyzed in 8848 metagenome-assembled high-quality phages from 104 fecal samples using single-molecule real-time sequencing. The results demonstrate that 97.60% of gut phages exhibit methylation, with certain factors correlating with methylation densities. Phages with higher methylation densities appear to have potential viability advantages. Strikingly, more than one-third of the phages possess their own DNA methyltransferases (MTases). Increased MTase copies are associated with higher genome methylation densities, specific methylation motifs, and elevated prevalence of certain phage groups. Notably, the majority of these MTases share close homology with those encoded by gut bacteria, suggesting their exchange during phage-bacterium interactions. Furthermore, these MTases can be employed to accurately predict phage-host relationships. Overall, the findings indicate the widespread utilization of DNA methylation by gut DNA phages as an evasion mechanism against host defense systems, with a substantial contribution from phage-encoded MTases.