Professor of Molecular Epidemiology.
Associate Director for Research and Graduate Education, Allen School.
Director, Immunology and Infectious Disease Graduate Program
- Paul G. Allen School for Global Animal Health, http://globalhealth.wsu.edu/
- Affiliate faculty, Department of Veterinary Microbiology, http://vmp.vetmed.wsu.edu/
- Affiliate faculty, School of Molecular Biosciences, http://www.smb.wsu.edu/
- Affiliate faculty, School of Electrical Engineering and Computer Science, https://school.eecs.wsu.edu/
- Adjunct faculty, Nelson Mandela African Institution of Science and Technology, http://www.nm-aist.ac.tz/
- Fellow, American Association for the Advancement of Science
- Member, Washington State Academy of Sciences
- Member, American Society for Microbiology
- Lifetime member, Northwest Scientific Society
BiographyDr. Call is a professor of molecular epidemiology in the WSU Paul G. Allen School for Global Animal Health. In 2014, he became a Fellow with the American Association for the Advancement of Science in recognition for his contributions to food and water safety, particularly through molecular epidemiology of antibiotic resistant bacteria in agricultural systems (including aquaculture). Dr. Call has published over 190 peer-reviewed papers and has ongoing antibiotic resistance research projects in the U.S., Tanzania, Kenya, Brazil, and Guatemala with support from the NSF, NIH, USDA, CDC, and the Allen School. He has consulted for the Gates Foundation and Fleming Fund regarding antibiotic resistance, and he was recently appointed to the Washington State Academy of Sciences. Dr. Call is a member of the Washington Global Health Pacific Northwest Antimicrobial Resistance Coalition, the Washington State Antimicrobial Resistance Working Group, and the Antimicrobial Resistance Steering Committee for the American Society for Microbiology. He was recently awarded the 2017 Washington State University Sahlin Faculty Excellence Award for Research, Scholarship and Arts, and was selected to give the Distinguished Faculty Address at Washington State University in 2017. He has served on grant review panels for NIH, NSF, USDA, USDA-ARS, and for several foundations.
Personal StatementAntibiotic resistance is one of the greatest global health challenges of our time – it is also the ultimate “externality” and one of the most “wicked problems” imaginable. Buried in the complexity of this challenge, however, are tremendous opportunities to work-the-problem and devise rationale solutions to limit the evolution, amplification, persistence, and dissemination of resistant bacteria in agriculture and in our hospitals and communities worldwide. It takes a multidisciplinary perspective, which is why I am grateful to have so many wonderful collaborators in the biological, engineering, mathematical and social sciences. I am firmly convinced that it is possible to devise solutions that benefit public health, consumers, producers and animal welfare. And, as a proud father of three living on an idyllic Palouse hobby farm, I am driven to find these solutions so that others can prosper and pursue fulfilling lives.
Education and Training1987, BS, Wildlife Management, Washington State University
1992, MS, Wildlife Management, Humboldt State University
1997, PhD, Zoology, Washington State University
1997-1999, Postdoctoral Fellow, Immunopathology, University of Michigan, Ann Arbor, MI
1999-2000, Postdoctoral Fellow, Pacific Northwest National Laboratory, Richland, WA
General Research / Expertise
My lab has expertise that spans molecular biology to epidemiology. My work includes both people and food animals, with a focus on the human-animal interface when feasible. The topics of interest are related to different aspects of antibiotic resistance including:
- Understanding evolution, regulation, and function of antibiotic-resistance genes;
- Comparative analysis of plasmids (small pieces of DNA that are shared between bacteria, often encoding antibiotic resistance);
- Developing strategies for manipulating the fitness cost of antibiotic-resistance genes;
Developing strategies for displacing pathogenic and antibiotic-resistant bacteria (e.g., by using probiotics);
- Developing alternatives to medically important antibiotics for use in people or animals;
Understanding the fate and transport of antibiotic residues in the environment and developing mitigation strategies;
- Developing strategies to disrupt or otherwise damage wound biofilms to increase the efficacy of medically-important antibiotics, or to eliminate the need for these antibiotics;
- Characterizing the epidemiology of antimicrobial resistance with particular attention to developing strategies to mitigate the evolution, amplification, persistence and dissemination of antibiotic-resistant bacteria.
My research can be applied in a number of ways.
Our work on the epidemiology of antibiotic resistance in low-income countries (Kenya, Tanzania, and Guatemala) helps to understand the primary risk factors for carriage of antibiotic-resistant bacteria. Most people will assume that using antibiotics, per se, will be the most important driver of this problem. Nevertheless, we have found that environmental transmission does a far better job of predicting carriage of antibiotic resistant microbes (enteric at least). One immediate implication of these findings is that controlling the use of antibiotics (call “stewardship”) is unlikely to have a significant effect on antibiotic resistance without serious attention to sanitation and hygiene. Improvements in these factors reduces transmission of resistant bacteria and pathogens, which in turn has tremendous benefits to human health while decreasing the incidence of illness and demand for antibiotics. Without investment in sanitation and hygiene within these communities, they will remain hotspots for emergence and dissemination of resistant bacteria to other parts of the world.
Our work on the fate and transport of antibiotic residues demonstrates that some antibiotics cause more harm by selectively favoring resistant bacteria in the environment, while other antibiotics cause less harm because these compounds are quickly adsorbed to soil particles and do not affect environmental bacteria. In the latter case, it is possible to detect these residues analytically, but they are not bioavailable and thus are irrelevant. We (and others) have also shown that composting is very effective at either destroying antibiotics or by providing high surface area of charged surfaces that adsorb antibiotic residues. Collectively, these findings demonstrate how we can adopt “best practices” through appropriate selection of antibiotics and waste management systems to limit the immediate or long-term impact of antibiotic residues in production environments. We are also investing strategies to incentivize producers to make best practice decisions.
Our work in Tanzania demonstrates that Maasai pastoralists, and probably many other milk-dependent rural households, ingest a considerable number of antibiotic-resistant bacteria when consuming milk. In the case of Maasai we face an added challenge from cultural reluctance to boil milk. As a consequence, we are testing ideas to introduce pasteurization at these households using “smart” thermometers. These thermometers serve as a valuable tool by recording “heating events” for research, but also make it very simple to control milk temperature when heating over a fire in a dark building. Preliminary tests indicate that this intervention is popular, but the effectiveness of the intervention depends on how it is introduced at the household level.
Our work in aquaculture, in close collaboration with Dr. Ken Cain at the University of Idaho, has supported the development and characterization of a live-attenuated vaccine for coldwater disease in salmonids, and characterization of the mechanism that is responsible for a probiotic that limits mortality from coldwater infections. Our work on biofilms, in close collaboration with Dr. Haluk Beyenal, demonstrates how it is possible to damage wound biofilms in such a way that conventional antibiotics are more effective against the biofilm communities residing in these wounds, but to also employ electrochemical processes to produce low but constant concentrations of biocides (e.g., hydrogen peroxide) that are capable of killing biofilm communities without damaging host tissue. In another project we are working with a small company, I2 Vapor, to determine how vaporized elemental iodine can be used to disinfect water and strip biofilms from surfaces. Such a technology holds considerable promise to effectively clean water and hoses on farms, thereby reducing the chances for exposure to pathogens from these sources. That is, we can help reduce the demand for antibiotics by decreasing the probability that animals will ingest pathogens (not to mention other benefits that accrue from such activities including improved animal welfare).
Finally, our work on proteinaceous alternatives to conventional antibiotics may lead to development of new classes of drugs that can be used in human or veterinary medicine. If the latter, that would result in less demand for medically-important antibiotics in food animal agriculture and companion-animal medicine. Everyone “wins” in such a scenario.
We are also beginning preliminary work to explore research opportunities about antibiotic-prescription guidelines (i.e., how to better use antibiotics) and to examine the potential negative (or positive) microbiome changes associated with antibiotic use by people.
Studying the epidemiology of antibiotic resistance helps us understand how resistant bacteria are shared within and between communities, and identify the risk factors associated with different cultural practices, living situations and environmental conditions. As an example, work from my lab in a high-density urban slum (in Kenya) found that having a shared hand-wash station represents a risk for carriage of antibiotic-resistant E. coli. This seems like a counterintuitive finding until you see the sanitation problems with these wash stations. These are, in fact, fomites for transmission (and a tractable intervention). In northern Tanzania we discovered that the Maasai preference for consuming raw milk is a significant risk factor for carriage of antibiotic-resistant E. coli, but the risk is even greater for those who boil milk. This counterintuitive finding is most likely due to the fact that boiled milk is a fantastic growth medium for bacteria. After boiling, milk is frequently placed in contaminated containers and may sit for hours, which is sufficient for orders-of-magnitude increases in the number of bacteria that are subsequently ingested. If, however, a household boils multiple liters of milk on a daily basis, the risk goes down. This interaction occurs because when there is sufficient milk, households make butter. Butter production on a wood fire involves multiple boiling events and consumption of the remaining “non-fat” milk when finished. That means “boiling households” produce a thoroughly sanitized product that is a poor growth medium while boiling households also exhibit a willingness to substitute milk products. These are just a couple of ways in which cultural context, living situations and environmental conditions can serve as important proximate drivers for carriage of antibiotic resistant bacteria in diverse communities. Our work continues in this area with funding from the CDC to work with hospitals and the communities in Kenya. We have a similar project already underway in Guatemala (funded through the Allen School). I am currently helping the CDC develop what we are calling a “core protocol” for establishing studies such as these in other countries in a manner that maximizes our ability to compare results across studies.
I am collaborating with colleagues both at WSU and at other institutions to develop new mathematical models of transmission. These are important efforts both because we can take advantage of data from our large field studies to produce validated models of transmission, but also because these models will inform both intervention efforts and help us to design more effective projects in the future. One example is the use of diffusion-based models for the persistence and dissemination of antibiotic-resistant bacteria in high density communities. Oddly, no one has ever approached this question with a classic diffusion framework and it offers many advantages compared to compartmentalized models. One advantage is that we can introduce spatial-temporal complexities and then pose questions about magnitude of change that is needed to limit different transmission pathways.
Selecting against antibiotic resistance.
Antibiotic resistance can persist in a population in the absence of antibiotic use. This happens in part because most resistance traits impose little to no fitness cost on the host bacterium and therefore there is little competitive disadvantage to harboring these traits. My lab has been investigating the possibility of artificially “tricking” bacteria into expressing genes when they are not needed as a way to increase fitness cost. For example, I am currently funded (NIH-R21) to determine if we can modify tetracycline antibiotics to make them ineffective as antibiotics, but still capable of triggering expression of tetracycline efflux pumps. In doing so, it appears that we are able to weaken the membrane integrity of tetracycline-resistant E. coli without harming tetracycline-sensitive E. coli. With this technology it may be possible, for example, to feed livestock the modified drug as a means to selectively reduce the background of tetracycline-resistant bacteria in these animals (and presumably have fewer such bacteria in the environment). There are other possible targets for this strategy and my lab will continue working to develop this narrative.
Alternatives to antibiotics.
From a medical perspective, the “arms race” against antibiotic resistance suffers from a diminishing number of viable options for attacking bacterial pathogens. Further complicating this issue is the need for medically important antibiotics in veterinary medicine. My lab has discovered two protein toxins (microcin PDI and entericidin) that are effective at killing either pathogenic E. coli and Shigella, or killing an important bacterial pathogen of coldwater aquaculture (Flavobacterium psychrophilum), respectively. Recently we initiated a collaborative project with colleagues at the Fred Hutch Cancer Center in Seattle to assess the feasibility of other protein antimicrobials.
My lab has worked on a variety of sequence-based projects, but I have only recently began developing the capacity to take advantage of this technology as a “big data” source. One example is the nearly completed effort to sequence 1,300 bacterial genomes from an NSF project in Tanzania. This data will allow us to launch a number of hypothesis-based projects about the genetic relationships between these strains, niche specificity and degree of intra-strain sharing of antibiotic-resistance plasmids.
With the discovery that milk is a risk factor for transmission of antibiotic-resistant bacteria in Tanzania, we have initiated an effort to help people “pasteurize” milk and maintain hygienic conditions with their products. Part of this effort includes test deployment of a prototype digital thermometer that was developed by two undergraduates and one of my post-doctoral fellows here at WSU. In a separate effort, we are looking at methods to disrupt biofilms. Biofilms bacterial communities that are encased in a self-produced matrix of proteins, carbohydrates, nucleic acids and water. These structures block antibiotic access to the encased bacteria. I have worked extensively with a colleague in Chemical Engineering to develop methods that can disrupt these biofilms and enhance penetration of antibiotics (funded by DoD). One approach uses an electronic scaffold of carbon fibers to electrochemically convert dissolved oxygen into hydrogen peroxide that subsequently attacks the biofilm. Another effort focuses on treating biofilms with a hypertonic concentration of osmotic compounds to disrupt the biofilm structure and allow better penetration of antibiotics. Finally, my lab is working with a novel iodine diffusion technology that holds promise both for sanitizing water while leaving trace concentrations of iodine, and to remove biofilms from hoses and other fluid delivery systems.
- Liu J, Zhao Z, Orfe L, Subbiah M, Call DR. (2016) Soil-borne reservoirs of antibiotic-resistant bacteria are established following therapeutic treatment of dairy calves. Environ Microbiol. 18(2):557-64. doi: 10.1111/1462-2920.13097. PMID: 26486254
- Omulo S, Thumbi SM, Lockwood S, Verani JR, Bigogo G, Masyongo G, Call DR. (2017) Evidence of superficial knowledge regarding antibiotics and their use: Results of two cross-sectional surveys in an urban informal settlement in Kenya. PLoS One. 12(10):e0185827. PMID: 28968447 PMCID: PMC5624622
- Schubiger CB, Orfe LH, Sudheesh PS, Cain KD, Shah DH, Call DR. (2015) Entericidin is required for a probiotic treatment (Enterobacter sp. strain C6-6) to protect trout from cold-water disease challenge. Appl Environ Microbiol. 81(2):658-65. doi: 10.1128/AEM.02965-14. PMID: 25381243 PMCID: PMC4277587
- Subbiah M, Mitchell SM, Call DR. (2016) Not All Antibiotic Use Practices in Food-Animal Agriculture Afford the Same Risk. J Environ Qual. 45(2):618-29. doi: 10.2134/jeq2015.06.0297. PMID: 27065409
- Sultana ST, Atci E, Babauta JT, Falghoush AM, Snekvik KR, Call DR, Beyenal H (2015) Electrochemical scaffold generates localized, low concentration of hydrogen peroxide that inhibits bacterial pathogens and biofilms Sci Rep 5 PMID: 26464174 PMCID: PMC4604468
- WSU looks for practices to thwart antimicrobial resistance
- Grad student pursues infectious diseases solutions
- Resisting The Resistance
- Researchers named to Washington State Academy of Sciences
- Fighting infection a new, old way
- Controlling the Spread of Diseases Among Humans, Other Animals and the Environment
- New Way Revealed for Antibiotic Resistance to Spread
2006-2009, Caroline Engle Faculty Fellow
2009-2013, Caroline Engle Distinguished Professor of Research on Infectious Diseases
2010, Awarded Honorary Life Membership to the Northwest Scientific Society
2011, Honors College Faculty Thesis Advisor of the Year award
2013, Zoetis Animal Health Award for Research Excellence
2014, Fellow, American Association for Advancement of Science. Awarded for contributions to food and water safety, particularly through molecular epidemiology of antibiotic resistant bacteria in agricultural systems.
2015, Washington State University Honors Faculty Award for Excellence in Scholarship
2017, Washington State University Distinguished Faculty Address
2017, Washington State University Sahlin Faculty Excellence Award for Research, Scholarship and Arts
2017, Elected to membership in the Washington State Academy of Sciences.