Decoding bacterial genomes using single-cell genomics

The human microbiome plays a critical role in our health, influencing everything from disease development to treatment responses. This connection has captured the attention of scientists worldwide, eager to unlock its secrets.  While traditional metagenomics has provided valuable insights, it falls short in resolving microbial diversity at the strain level and accurately profiling genes involved in antibiotic resistance. These limitations highlight the need for more advanced approaches.

To address this, a team of researchers led by Associate Professor Masahito Hosokawa, from Waseda University, in collaboration with bitBiome, Inc., developed a groundbreaking single-cell genome approach. This approach, which reads information from individual cells, offers a promising alternative to conventional metagenomics. This study, published in Microbiome on 02 October 2024, explores the microbial diversity and genetic features using single-cell genomic analysis.

“The limitation of metagenomics inspired us to develop a new approach to explore the human microbiome at the single-cell level. This single-cell genome approach can enhance our understanding of how bacteria interact and exchange genetic material including antibiotic resistance genes, providing deeper insights into human health and disease,” says Hosokawa.

The researchers conducted a large-scale individual analysis of microbes in the human body. For this, they recruited 51 participants and collected their saliva and fecal samples. They then performed a new single-cell genome analysis method called SAG-gel technology, commercialized as bit-MAP® by bitBiome, Inc. In this technique, individual bacteria were enclosed in a gel and their genomes were amplified and analyzed individually.

The researchers recovered genomes of 300 bacterial species using this novel technique which were missed by the conventional method. In addition, the new technique provided deeper insights into antibiotic resistance genes, gene exchange networks, bacterial interaction, and diversity.

“Our study analyzed 30,000 individual genomes of oral and intestinal bacteria, which is the world's largest genome dataset, showcasing the power of single-cell genomics in elucidating microbial diversity and interactions,” says Hosokawa.

The findings of this study have several potential applications. In public health, the detailed profiling of antibiotic resistance genes can help develop more targeted and effective treatment strategies. This in turn can help prevent diseases, reduce healthcare costs, and improve public health. In environmental monitoring, single-cell genomics can track genetic shifts across ecosystems to manage and prevent the spread of antibiotic resistance. In the agricultural sector, understanding antibiotic resistance gene dynamics can guide practices to minimize resistance spread through soil, water, and livestock.

The study highlights the transformative potential of single-cell genomics in microbiome research, offering a more detailed and nuanced understanding of microbial communities.

“Our approach provides clues to better understand how antibiotic resistance spreads in bacteria and has potential for future medical and public health applications,” concludes Hosokawa.

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Reference

DOI: 10.1186/s40168‑024‑01903‑z

Authors: Tetsuro Kawano‑Sugaya¹, Koji Arikawa^1,2, Tatsuya Saeki¹, Taruho Endoh¹, Kazuma Kamata¹, Ayumi Matsuhashi¹, and Masahito Hosokawa^1,2,3,4,5*

Affiliations      

¹bitBiome, Inc., Japan

²Department of Life Science and Medical Bioscience, Waseda University, Japan

³Computational Bio Big-Data Open Innovation Laboratory, National

Institute of Advanced Industrial Science and Technology, Japan

⁴Institute for Advanced Research of Biosystem Dynamics, Waseda

Research Institute for Science and Engineering, Japan

⁵Research Organization for Nano and Life Innovation, Waseda University, Japan

About Waseda University
Located in the heart of Tokyo, Waseda University is a leading private research university that has long been dedicated to academic excellence, innovative research, and civic engagement at both the local and global levels since 1882. The University has produced many changemakers in its history, including nine prime ministers and many leaders in business, science and technology, literature, sports, and film. Waseda has strong collaborations with overseas research institutions and is committed to advancing cutting-edge research and developing leaders who can contribute to the resolution of complex, global social issues. The University has set a target of achieving a zero-carbon campus by 2032, in line with the Sustainable Development Goals (SDGs) adopted by the United Nations in 2015. 

To learn more about Waseda University, visit https://www.waseda.jp/top/en  

About Associate Professor Masahito Hosokawa
Dr. Masahito Hosokawa is an Associate Professor at Waseda University and the Chief Scientific Officer at bitBiome, Inc. He earned his Ph.D. in Engineering from Tokyo University of Agriculture and Technology. With over a decade of experience, he has authored numerous publications, focusing on single-cell analysis, genomics, and microfluidics. He has received several prestigious awards, including the Young Scientists' Award by MEXT in 2019 and the Minister’s Award under the Award for Academic Startups 2022 program.