Global microbiome study uncovers thousands of new species, maps urban antimicrobial resistance, reveals new drug candidates

According to a study by the International MetaSUB Consortium, a global microbe tracking effort led by Weill Cornell, approximately 12,000 bacteria and viruses collected from a sample of transit systems and hospitals around the world between 2015 and 2017 did not had never been identified. Medical researchers.

For the study, published May 26 in Cell, international investigators collected nearly 5,000 samples over a three-year period in 60 cities in 32 countries and six continents. The researchers analyzed the samples using a genomic sequencing technique called shotgun sequencing to detect the presence of various microbes, including bacteria, archaea (single-celled organisms distinct from bacteria) and viruses that use l DNA as genetic material. (Other types of viruses that use RNA as genetic material, such as SARS-CoV-2, the virus that causes COVID-19, would not have been detected with the DNA analysis methods used. in this pre-pandemic study.)

This area of ​​research has important implications for detecting outbreaks of known and unknown infections and for studying the prevalence of antibiotic-resistant microbes in different urban settings.

“Every time you sit on the subway, you’re probably walking around with an entirely new species,” said lead author Dr Christopher Mason, co-director of the WorldQuant Initiative for Quantitative Prediction and professor of physiology and biophysics at Weill Cornell Medicine. . Dr Mason is also a co-founder and paid consultant for Biotia and Onegevity Health, and a paid speaker for WorldQuant LLC.

The current study has led to the discovery of 10,928 viruses and 748 bacteria that are not present in any reference database.

Dr Mason founded MetaSUB (short for Metagenomics and Metadesign of Subways and Urban Biomes) in 2015, along with Dr Evan Afshin, who was then an undergraduate student at Macaulay Honors College at Queens College and is now a researcher in physiology and biophysics. at Weill Cornell Medicine and paid consultant for Onegevity Health. The recently published study was led by Drs. Mason, David Danko, a Weill Cornell Graduate School doctoral student in Dr. Mason’s lab during the study, and Daniela Bezdan, who was a computational biomedical research associate at Weill Cornell Medicine at the time.

By collecting samples of microbes and analyzing their genes – collectively called the microbiome – researchers hope to learn more about bacteria, viruses and other microorganisms that live in humans. For example, research can help identify the emergence of strains resistant to antibiotics. Predicting antibiotic resistance from genetic sequences alone is a challenge, but researchers were able to map some genes known to be linked to resistance, quantify their abundance, and confirm the ability of genetic markers to confer resistance. They found that some cities had more resistance genes than others and that there may be city-specific signatures for some of these genes.

Antimicrobial resistance remains a major challenge for global health. “While more research is needed, this dataset demonstrates the value and potential of microbiome mapping and monitoring, and the information it can provide to physicians, scientists and public health officials. “Said Dr Afshin.

In addition, knowledge of the small molecules and proteins made by microbes could also lead to the discovery of new antibiotics as well as other molecules that could be developed as drugs. Many antibiotics and drugs currently in use come from microbial sources. Discoveries made in new microbial species could also lead to new laboratory tools and approaches, such as new ways to use the molecular editing tool known as CRISPR. In this study, the researchers found 838,532 new CRISPR arrays – extracts of viral DNA found inside bacteria – and 4.3 million new peptides (small proteins).

As a result of these sampling efforts, Dr Mason said he could predict with about 90% accuracy where a person lives, simply by sequencing the DNA on their shoes. Many factors have been found to influence a city’s microbiome, including overall population and population density, elevation, proximity to the ocean, and climate. The findings on these separate signatures could allow for future forensic studies.

“A microbiome contains molecular echoes of where it was collected. A coastal sample can contain salt-loving microbes while a sample from a densely populated city can show striking biodiversity,” said the Dr Danko.

Drs. Mason and Afshin began collecting and analyzing microbial samples in the New York City subway in 2013. After posting their first results, dubbed PathoMap, they were contacted by researchers around the world who wanted to do similar studies for their own cities. International interest inspired Dr Mason’s lab to create MetaSUB and recruited Daniela Bezdan as research director. “We needed internationally accepted protocols, logistics and collaborative arrangements with scientists, vendors, government offices and philanthropic foundations for potentially 100 cities in 20 countries,” Bezdan said.

Today, MetaSUB continues to grow and has expanded to collect RNA and DNA samples from air, water and wastewater, in addition to hard surfaces. This led to a $ 5 million grant for wastewater sequencing and viral monitoring in three states (Florida, New York, and Wisconsin), and which is part of the New National Wastewater Monitoring System (NWSS) of the Center for Disease Control and Prevention.

The group also oversees projects such as the World Cities Sampling Day (gCSD), which is held annually on June 21, and has conducted large-scale studies, including a comprehensive microbial analysis of Rio de Janeiro before, during and after the 2016 Summer Olympics. Many of the samples analyzed in the current study were collected during World City Sampling Day in 2016 and 2017. The sampling effort in New York was conducted with support from the Weill Cornell Medicine Clinical and Translational Science Center (CTSC), in conjunction with CTSC Senior Program Director Jeff Zhu. Dr Mason and his colleagues are currently preparing for this year’s event.

“When we started in 2015, the consortium consisted of 16 cities; six years later, we have over 100 cities. It’s great to have this curious, self-reliant and enthusiastic group of co-researchers, ”said Dr Mason, who is also a professor of computational genomics in computational biomedicine at the SAR Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute. for Computational Biomedicine at Weill Cornell Medicine.

“Although samples are collected all over the world, a lot of the testing is done right here in New York City at Weill Cornell Medicine,” said Dr. Mason. Sequence analysis and assembly also leveraged Bridges and Bridges-2, Extreme Science and Engineering Discovery Environment (XSEDE) supercomputers at the Pittsburgh Supercomputing Center. Researchers at MetaSUB in Switzerland (Drs. Andre Kahles and Gunnar Rätsch) used these assemblies and raw data to construct a searchable Global DNA Sequence Portal (MetaGraph) that indexed all known genetic sequences (including MetaSUB data). ). The portal maps all known or newly discovered genetic elements to their location on Earth and can aid in the discovery of new microbial interactions and putative functions.

The isolation of DNA from samples has been largely performed with support from Zymo Research and Promega, and sequenced in collaboration with Dr Shawn Levy of the HudsonAlpha Institute for Biotechnology, Dr Klas Udekwu of Stockholm University and the New York Genome Center. Future and ongoing studies will examine RNA and DNA with long reads and spatial imaging methods, as well as trace metabolites from global sites, and continue to update the genetic map at the planetary scale.

About Hector Hedgepeth

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