An international consortium of researchers created a global atlas of microbes from 60 cities over three years using swabs from subway surfaces, cataloguing detailed information on the locations and characteristics of bacteria, viruses and archaea, including thousands of microbial species not found in current reference databases.
The study, published Wednesday in Cell, is the largest-ever metagenomic analysis of urban microbes, and has wide implications for controlling outbreaks of pathogenic infections and studying antimicrobial resistance.
"[Subways] can have a rich treasure trove of new biology, new species and even new therapeutics," said Christopher Mason, a professor of genomics, physiology and biophysics at Weill Cornell Medicine. Mason kickstarted the project with an earlier study on microbes in the subway. After its publication, researchers from around the world reached out to him, interested in the microbial profiles of their own cities.
While new variants of the virus that causes COVID-19 continue to make headlines, all microbes, even harmless ones, go through rapid reproduction and evolution to form new strains. Humans are also known to have a significant impact on the microbes found in the environment, so places with dense populations such as cities tend to have diverse pools of microbes. These factors together contribute to a unique microbial footprint for each city.
"Every city has its own 'molecular echo' of the microbes that define it," Mason said. "If you gave me your shoe, I could tell you with about 90% accuracy the city in the world from which you came."
Growing interest in identifying these microbial footprints around the world drove Mason to form the International MetaSUB Consortium, short for Metagenomics and Metadesign of Subways and Urban Biomes, which now contains researchers working on six continents.
Over three years, researchers from the consortium collected samples from the surfaces of mass-transit systems like subways and buses, looking to target areas where the most people congregate. The researchers used a deceptively simple protocol developed by Mason to collect the samples.
"If you've used a Q-tip before, you can come help us swab," Mason said. "It's like swabbing the city to see what microbes and other DNA is present. It is like Google Maps for DNA."
The final analysis was based on 4,728 samples, taken from 60 cities on six continents — every one but Antarctica. The analysis and sequencing was done primarily on a supercomputer in Pittsburgh operated by the Extreme Science and Engineering Discovery, a National Science Foundation-funded virtual organization that coordinates the sharing of data and computing power between scientists.
The results revealed microbes unique to each city. There were also 31 species that were found in 97% of samples, all of which were distinct from the microbes that live on humans.
But the researchers did more than just round up species. The group identified over 800,000 new CRISPR arrays, repeated segments of DNA that are the foundation for modern gene editing. The findings could also contribute to the fight against infectious diseases by identifying potential new sources of antibiotics, which are typically derived from microbes.
"This provides us a rich substrate of new possible drugs and small molecules, and it helps us create infrastructures and tools to map emerging viruses," Mason said.
Separate from the study itself, the researchers have made their data publicly available in the form of several interactive online maps. One map allows users to search for microbes by city or by species. Another allows users to search for a city and see a list of drug-resistant microbes that have been identified there. And because they exist online, these maps can be updated as new data becomes available.
Mason and his team at Weill Cornell are now working on validating some of the potential drug targets and exploring their therapeutic properties. The colleagues are also working on increasing the scope of their findings by swabbing for RNA, as the present study only focused on DNA. The team is also interested in applying its findings to tracking COVID-19.
"This links to ongoing efforts to map COVID, such as in hospitals and cities, and can establish a baseline for cities if there is a calamity like a fire or flood," Mason said. Such a calamity could radically change the microbial landscape of a city, which could have implications for disease prevention.
The consortium at large is working on several new projects, including an analysis of the prevalence of SARS-CoV-2 and other coronaviruses in cats. It is also preparing for an analysis of the 2021 Tokyo Olympics, which will examine the microbial populations of the city before, during and after the event, which is expected to attract almost 80,000 people from overseas.
For now, Mason hopes that in addition to their practical applications, the findings will encourage a richer understanding of the complex microbial communities present in any city.
"People often think a rainforest is a bounty of biodiversity and new molecules for therapies, but the same is true of a subway railing or bench," Mason said.
The study, "A global metagenomic map of urban microbiomes and antimicrobial resistance," published May 26 in Cell, was authored by David Danko, Weill Cornell Medicine, Alsaud Institute for Computational Biomedicine and Jagiellonian University; Daniela Bezdan, Weill Cornell Medicine, Alsaud Institute for Computational Biomedicine and Universitätsklinikum Tübingen; Evan E. Afshin, Chandrima Bhattacharya, Daniel J. Butler, Daisy Donnellan, Katelyn Jackson, Katerina Kuchin, Abigail Lyons, Lauren Mak, Dmitry Meleshko, Krista A. Ryon, Jorge L. Sanchez, Heba Shaaban, Maria A. Sierra, Dominique Thomas, Ben Young, Josue Alicea, Ana M. Cañas, Aspassia D. Chatziefthimiou, Iman Hajirasouliha, Jaden J.A. Hastings, Kaymisha Knights, Cem Meydan, Brandon Valentine, Christopher E. Mso and Jifeng Zhu, Weill Cornell Medicine and Alsaud Institute for Computational Biomedicine; Sofia Ahsanuddin, Ichan School of Medicine at Mount Sinai; Kern Rei Chng, Amanda Ng, Eileen Png and Niranjan Nagarajan, Genome Institute of Singapore; Jochen Hecht, Barcelona Institute of Science and Technology; Mikhail Karasikov, Harun Mustafa and Gunnar Rätsch; ETH Zurich, University Hospital Zurich and Swiss Institute of Bioinformatics; Beth Mutai, Barcelona Institute for Science and Technology and Kenya Medical Research Institute; Russel Y Neches, Nikos C. Kyrpides, David Paez-Espino, Lawrence Berkeley National Laboratory; Olga Nikolayeva and Tatyana Nikolayeva, independent researchers; Omar O. Abudayyeh, Dennis Gankin and Jonathan S. Gootenberg, Massachusetts Institute of Technology; Malay Bhattacharyya and Ran Blekhman, University of Minnesota; Eduardo Castro-Nallar, Universidad Andres Bello; Robert W. Crawford, California State University; Francesca De Filippis and Danilo Ercolini, University of Naples Frederico II; Youping Deng, University of Hawaii; Christelle Desnues, Aix-Marseille Université; Emmanuel Dias-Neto, A.C. Camargo Cancer Center; Marius Dybwad; Norwegian Defence Research Establishment FFI; Eran Elhaik, Lund University; Alina Frolova, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine and Kyiv Academic University; Alexandra B. Graf, University of Applied Sciences Vienna; David C. Green, Frank J. Kelly and Gabriella Mason-Buck, Imperial College London; Mark Hernandez, Marina Nieto-Caballero and Denise Syndercombe Court, University of Colorado Boulder; Gregorio Iraola, Institut Pasteur de Montevideo, Universidad Mayo and Wellcome Sanger Institute; Soojin Jang, Institut Pasteur Korea; Andre Kahles, ETH Zurich, Kyiv Academic University and Universidad del Desarrollo; Pawel P. Labaj, State Key Laboratory of Genetic Engineering (SKLGE) and MOE Key Laboratory of Contemporary Anthropology; Patrick K.H. Lee and Marcus H.Y. Leung, City University of Hong Kong; Per O. Ljungdahl, Stockholm University; Ken McGrath, University of Queensland; Emmanuel F. Mongodin and Lynn M. Schriml, University of Maryland; Milton Ozorio Morales, Fundação Oswaldo Cruz; Houtan Noushmehr, Universidade de São Paulo; Manuela Oliveira, Universidade do Porto; Stephan Ossowski, Barcelona Institute of Science and Technology and Universitätsklinikum Tübingen; Olayinka O. Osuolale, Elizade University, Orhan Özcan and Osman U. Sezerman, Acibadem Mehmet Ali Aydınlar University; Nicolás Rascovan, Institut Pasteur; Hugues Richard; Sorbonne Université and Robert Koch Institute; Torsten Semmler, Robert Koch Institute; Leming Shi, Fudan University and State Key Laboratory of Genetic Engineering (SKLGE) and MOE Key Laboratory of Contemporary Anthropology; Tieliu Shi and Jun Wu, East China Normal University; Rania Siam, West Indies and American University in Cairo; Le Huu Song, 108 Military Central Hospital and Vietnamese-German Center for Medical Research; Haro Suzuki, Keio University; Scott W. Tighe, University of Vermont; Kias I. Udekwu, Stockholm University and Swedish University of Agricultural Scienes; Juan A. Ugalde, Millenium Initiative for Collaborative Research on Bacterial Resistance and Universidad del Desarollo; Dimitar I. Vassilev; Sofia University; Elena M. Vayndorf; University of Alaska, Fairbanks; Thirumalaisamy P. Velavan, Universitätsklinikum Tübingen and Duy Tan University; Jun Wu; María M. Zambrano, Corporación CorpoGen Research Center; Sibo Zhu, State Key Laboratory of Genetic Engineering (SKLGE) and MOE Key Laboratory of Contemporary Anthropology and Fudan University.