Combating antibiotic resistance with data-driven surveillance

Since the world’s first broadly effective antibiotic arrived in 1928, bacteria have evolved new strategies to fight back against antibiotics. Current trends show that antibiotics are increasingly failing to prevent, treat, or cure bacterial infections. Some projections imply that by 2050, antibiotic resistance fatalities may outnumber those of cancer.

Virginia Tech researchers are using data-driven surveillance to learn more about the antibiotic resistant bacteria that are lurking in communities across Virginia and the world. The transdisciplinary team has been turning to the sewers to track a variety of existing and new pathogens, including SARS-CoV-2, with the goal of giving early warnings of outbreaks that are on the way to a community.

“Antibiotic resistance monitoring of sewage and water samples can help us figure out which communities have a problem and the immediate things that scientists and doctors can do to effectively combat antibiotic resistance,” said Amy Pruden, University Distinguished Professor in the Department of Civil and Environmental engineering in the College of Engineering. “This method can also give us insights into why certain communities have higher cases of antibiotic resistance.”

Pruden, who is also an affiliate of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens and of the Global Change Center, housed in the Fralin Life Sciences Institute at Virginia Tech, and a group of Virginia Tech researchers were recently awarded a National Science Foundation Research Traineeship grant called "Convergence at the Interfaces of Policy, Data Science, and Environmental Science and Engineering to Combat the Spread of Antibiotic Resistance.”

The goal of the traineeship is to provide science and technology-focused graduate students with the technical and professional skills, as well as a fluency in science-based policy, that are required to develop and launch successful wastewater surveillance for public health monitoring and protection.

Antibiotic resistance is an especially complex and multi-faceted problem that extends far beyond microbiology. In order to properly address the issue, researchers need to be well versed in how policies are implemented, competent at analyzing large-scale data, and will need to be able to navigate key ethical issues, like privacy.

Computer science is one discipline that is essential to understanding the complex problem of antibiotic resistance. According to Liqing Zhang, a professor in the Department of Computer Science in the College of Engineering, computer science students will benefit from interacting with students from other disciplines and learning how to tailor their skills to solving this real-world problem.

"They will bring to the table their computational skills that are needed for processing and analyzing large-scale biological, chemical, and environmental data," said Zhang. "The level of transdisciplinary work is unprecedented and will give every trainee a very comprehensive understanding of this important yet complex problem of antibiotic resistance."

One aspect of wastewater monitoring that trainees and researchers must be mindful of is privacy. Although community monitoring has enormous scientific promise, it raises quite a few concerns about confidentiality. For example, certain stigmas may be linked with illnesses and illegal recreational drugs may be detected through monitoring.

“The smaller the community or the more geospatially distinct the monitoring, the more likely the source of disease markers might be linked to specific clusters of homes, presenting challenges with respect to confidentiality,” said Leigh-Anne Krometis, an associate professor and Turner Faculty Fellow in the Department of Biological Systems Engineering, an affiliate of the Global Change Center and of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens, and co-principal investigator on the project.

What distinguishes this traineeship from others, according to Pruden, is that the students will be trained in stakeholder engagement and policy from the very beginning. Not only that, but the work they are doing will be applicable to real world problems, with real world solutions.

Aided by an army of eager students, Virginia Tech researchers will look to scale their antibiotic resistance monitoring through field projects in rural Appalachia, working with cutting-edge wastewater treatment facilities operated by the Hampton Roads Sanitation District in Southeast Virginia, and working in labs in several countries that are also seeking to advance wastewater surveillance for public health purposes.

Trainees will complete four training elements: A graduate certificate in Science, Technology, and Engineering in Policy (STEP), bootcamps and workshops, a field project, and a transdisciplinary dissertation chapter. They will address a critical demand for science-based policy training across the graduate curriculum at Virginia Tech, as well as regionally and worldwide.

The STEP courses are predicted to reach at least 200 master's and doctorate students over the course of five years of the grant. Around 75 students are expected to obtain the graduate certificate, which is broadly targeted toward students who are interested in understanding policy processes and enhancing their capacities to engage with decision-makers and other stakeholders.

“This is a really wicked problem that calls for transdisciplinary, collaborative responses,” said Todd Schenk, an associate professor in the School of Public and International Affairs in the College of Architecture and Urban Studies, co-principal investigator on the project, and the founding director of the STEP program. “Scientists and technical experts are much more effective actors within policy processes when they are appreciative of how decisions are made, tuned in to the factors others are considering and why their priorities and logic may be wildly different from their own, and find ways to accommodate those differences.”

Schenk is also an affiliate of the Global Change Center and the Center for Coastal Studies.

Pruden and her colleagues have already tested a prototype of the proposed wastewater-based surveillance system in Blacksburg during the COVID-19 outbreak, with promising findings. The scientists have been collecting wastewater samples and measuring the RNA that is specific to the SARS-Cov-2 virus.

Antibiotic resistance monitoring, on the other hand, is significantly more challenging since there are many different bacterial pathogens of concern, and they may collectively contain thousands of antibiotic resistance genes in any one wastewater or water sample.

To advance this type of monitoring, graduate student trainees will collaborate with a transdisciplinary group of faculty to create a cyber-enabled system using shotgun metagenomic sequencing, which can broadly profile DNA from any microbes present in a sample. Various bioinformatic studies will be developed and used to discover antibiotic resistance genes.

With this huge quantity of data at their disposal, researchers can then look at the community and observe how that pattern changes over time.

“If we start equipping wastewater treatment plants with this kind of sequencing, we could identify what specific kind of antibiotic resistance is spiking in the community,” added Pruden. “In the future, this information could be made available and could provide guidance on whether there might be outbreaks of concern in a community.  It could also help doctors select which antibiotics are most likely to be effective to prescribe to patients.”

In addition to Krometis and Schenk, other researchers on the grant include Tiffany Drape, an assistant professor in the Department of Agricultural, Leadership, and Community Education in the College of Agriculture and Life Sciences; Marc Edwards, University Distinguished Professor in civil and environmental engineering in the College of Engineering; Peter Vikesland, the Nick Prillaman Professor of Civil and Environmental Engineering in the College of Engineering; Kang Xia, a professor of environmental chemistry in the School of Plant and Environmental Sciences; and Lenwood Heath, a professor in the Department of Computer Science in the College of Engineering.

If you are a student who is interested in participating in the National Science Foundation Research Traineeship grant, visit the website.