Iowa State Launches Research Initiative to Fight Antimicrobial Resistance

By Kristin Killian

Antibiotics are one of humankind’s greatest life-saving discoveries, but the rise of antibiotic resistance is now one of our biggest threats. A new research initiative at Iowa State University takes on the growing problem of antibiotic resistance, also called antimicrobial resistance (AMR), building teams of scientists from across areas of Iowa State’s longtime strengths – agriculture, biosciences, data science – to find solutions to AMR, a global grand challenge.

Complex AMR problem calls for “systems” approach

The AMR problem seems simple enough – and pretty scary: AMR is rapidly increasing, as more bacteria develop an ability to fight off the drugs that are used to stop them in their tracks. Illnesses that were once easily curable with antibiotics could soon become life-threatening. But the solution is not as simple as just developing different, stronger types of antibiotics.

Instead, AMR is a complicated challenge with both origins and impact in human health, animal health, and our environment – and in the connections between all three of those systems. Solving such complex problems requires interdisciplinary research that brings together expertise from the molecular- to ecosystem-level.

At Iowa State, more than 60 researchers from across campus have joined the AMR initiative, all dedicated to this “systems” approach that integrates better understanding of the biology of AMR organisms with our crop and animal agroecosystems and social and environmental effects.

“Iowa State is already home to diverse and highly experienced investigators in many aspects of AMR research, including strengths in animal models, data analysis and modeling, and discovery of new antimicrobials. The new initiative helps us ‘connect the dots’ between our researchers to move our AMR research in ambitious, innovative directions,” said Sarah Nusser, Iowa State vice president for research.

Four projects begin in critical AMR research areas

Iowa State’s AMR initiative recently awarded seed funding to four interdisciplinary projects in critical research areas:

New microsensor chip to help prescribe the right – and only the right – kind of antibiotic

Meng Lu, electrical and computer engineering, mechanical engineering; Qijing Zhang, veterinary microbiology and preventive medicine; Zengyi Shao, chemical and biological engineering

Using just the right antibiotic to target an infection – and minimizing the use of broad spectrum antibiotics – is key to slowing AMR. But current methods for determining what antibiotic is most effective take 1-3 days, too long to wait for most ill patients and their doctors, so broad spectrum antibiotics are often prescribed instead. A team of Iowa State researchers in the fields of engineering, veterinary medicine, and microbiology are speeding up the diagnostic process with a point-of-care system that will determine AMR profiles within just two hours. The core component is a microchip that integrates polymerase chain reactions and high-density microarray to simultaneously detect more than 700 drug-resident genes. The new technology will help health care make optimal treatment decisions and avoid the incorrect or unnecessary use of antibiotics.

Targeting DNA to slow tuberculosis bacteria’s path to AMR

Scott Nelson, biochemistry, biophysics, and molecular biology; Richard Honzatko, biochemistry, biophysics, and molecular biology; Bryan Bellaire, veterinary microbiology and preventive medicine

Tuberculosis infections are a leading cause of death worldwide, and the spread of multi-drug resistant strains of TB is on the rise. Preventing TB deaths will likely take a combination of next-generation antibiotics combined with new types of medications that slow TB bacteria’s mutation rate. A team of Iowa State researchers with expertise in enzymology, structural biology, and microbiology, will identify and test inhibitors against a type of DNA enzyme that often goes into mutation overdrive when exposed to antibiotics. The team’s work will help develop drugs that put the brakes TB’s path to AMR – and help stop the growing number of deaths from drug-resistant TB.

Mixing natural compound cocktails for new antibiotics

Gregory Phillips and Michael Wannemuehler, veterinary microbiology and preventive medicine; Byron Brehm-Stecher, food safety and human nutrition; Santosh Pandey, computer and electrical engineering; George Kraus, Levi Stanley, and Arthur Winter, chemistry

Despite the need for new antibiotics to combat emerging drug resistant bacteria, few new drugs have been approved for clinical use in the last three decades. To help identify new drugs, a transdisciplinary team of Iowa State researchers will characterize a class of compounds known as pyrones, which may hold promise for the development of new antimicrobials. The team combines the disciplines of chemistry, microbiology, and engineering and uses novel approaches in synthetic organic chemistry, computation, microbiology, and animal models to identify pyrone derivatives with the enhanced antimicrobial power needed to fight bacterial infection.

Tracking genes to identify threat of AMR in agroecosystems

Adina Howe, agricultural and biosystems engineering; Laura Jarboe, chemical and biological engineering; Catherine Logue, veterinary microbiology and preventive medicine; Nicole Ricker, USDA National Animal Disease Center and agricultural and biosystems engineering; and Heather Allen, USDA National Animal Disease Center

Understanding the spread of AMR in the lab is one thing, but measuring and studying AMR in our much more complex and dynamic environment is quite another – and a significant challenge. Iowa State experts in microbiology, bacterial genetics, and engineering will develop a probe that tracks mobility and acquisition of antimicrobial resistant genes in agroecosystems, a particularly important environment because of the prevalence of antibiotic use in food-producing animals and the transfer of AMR across the food chain. This study will help show how resistance genes move into previously non-resistant strains of bacteria and facilitate the development of new mitigation strategies for drug-resistant strains.

New AMR seed projects will receive up to $50,000 per year for two years, with a possibility of a third year of funding, to help position the teams to secure external funding to continue their work.

“These seed projects will jump-start new interdisciplinary approaches that address the complex, global problem of AMR and help ensure Iowa State continues its national and international leadership in the fight to emerging antibiotic resistant diseases,” said Nusser.

The AMR seed funding program is supported by Iowa State’s Office of the Vice President for Research, in partnership with the College of Agriculture and Life Sciences, and the College of Veterinary Medicine.