Wanli He:
Plasmids metagenomic: insight into their cryptic ecology

Date: 01-12-2022    Supervisor: Søren J. Sørensen, Joseph Nesme & Jakob Russel




Plasmids, act as sophisticated genetic parasites on bacteria life cycle, have a key role in bacterial ecology and evolution due to their mobility and cargo of diverse host-beneficial traits. In the past, studies on plasmids have mainly focused on single bacterial isolates or model plasmids due to the limitations of research methods, causing our understanding of plasmids is still limited, particularly at community level. Moreover, there are no systematic workflows for plasmid classification, plasmid host and gene annotation, and quantitative analysis corresponding to them, which is due to the absence of precise definitions for plasmid meta-analysis.

Therefore, the first step in this thesis is to define plasmid meta-analysis, design a systematic workflow corresponding to it (Manuscript Ⅰ). In the study, we benchmarked the state-of-art plasmid detecting tools by using simulated metagenomic datasets. Then, a plasmid analysis pipeline, Plaspline, was designed based on the selected tools, which showed a better performance on detecting plasmids due to a novel strategy that we developed for detecting and analyzing plasmid genomes from metagenomes.

The second step is to explore the plasmid world. Specifically, we focused on early life human gut to investigate the early colonization and establishment of the infant gut plasmidome, and linked plasmid to their own host by a novel strategy to analyze plasmid functions on bacterial host (Manuscript Ⅱ). Besides, we were also interested in the gut plasmidome of disease-related populations to reveal their role on gut microbial health (Manuscript III).

Excluding human gut, we also estimated the urban water plasmidome from three European countries to answer their dynamic along the water system by applying a combined metagenomic and meta-plasmid-DNA sequencing approach (Manuscript IV). Continually, we also analyzed plasmid antibiotic resistance genes (ARGs), and their impacts on microbiome and ecosystem ARGs in urban water systems (Manuscript V). Together, our works not only filled the research gap in the qualitative and quantitative plasmid meta-analysis methods, but also expanded current knowledge about plasmids in the human gut and urban water systems.