pts the cell membrane so fast that the bacteria does not even have time to develop resistance mechanisms.”
It’s fair to ask how safe this new nano-bactericide is for people, given some people’s concerns about the science of nanoparticles. Chitosan is favored as a drug-delivery material specifically because of its low toxicity to humans. But because materials sometimes behave differently when reduced to a nanoscale, testing for safety is important for understanding this material’s efficacy in treating infections in animals and humans. To investigate, Jeong and colleagues performed a risk assessment using animal models. The results showed that when used at concentrations strong enough to have antimicrobial effects, chitosan nanoparticles caused no toxicity to animal and human cells.
After figuring out the underpinnings of how chitosan nanoparticles work against pathogenic microorganisms, Jeong set his sights on how to harness this power to benefit agricultural animals and make animal-based foods safer for people.
Metritis and mastitis are two cattle diseases that plague dairy and beef farmers, costing them millions of dollars per year. Metritis is an infection of the uterine lining caused by multiple microbes. It can strike 20 to 40 percent of postpartum cows and it directly costs the U.S. dairy industry upwards of $600 million annually. Mastitis is an infection of a cow’s mammary tissues, or udder, and it is estimated to cost farmers $110 per cow in lost income.
Beef cattle on a northcentral Florida farm participating in one of Jeong's studies on interactions between livestock, the environment, and bacteria. (Courtesy of the Jeong lab.)
But worse than the lost revenue, cattle are experiencing an increase in multi-drug resistant bacteria relevant to these infection types. This is worrisome for human health too, because bacteria are adept at sharing genes useful to their survival. Jeong has sought to characterize the specific types of bacteria and drug resistance genes involved in these infections, in order to better fight them. Often working with UF College of Veterinary Medicine associate professor Klibs Galvao, Jeong challenged dogma concerning which uterine bacteria are responsible for causing metritis.
Jeong and Galvao’s teamwork revealed that applying chitosan nanoparticles to the infected uteri of cows drastically altered the microflora to a healthier composition. The particles were effective against pathogenic Fusobacteriaceae and Bacteroidaceae, both of which are associated with acute infectious processes and are resistant to penicillin-based antibiotics.
Jeong and his collaborator, Klibs Galvao, at a dairy cow research center where the pair are investigating novel ways of treating drug-resistant infections in food animals.
A recent $460,000 grant from the USDA National Institute for Food and Agriculture brings Jeong’s funding sum close to $1 million for investigating chitosan nanoparticles as a next-gen antimicrobial. His newest phase of inquiry will examine how to attach the best broad-spectrum antibiotics and drug extenders to chitosan nanoparticles to deliver a three-pronged infection-fighting punch directly to infection sites.
“We are very excited about testing this combination therapy,” Jeong says. “Medical doctors don’t have many antibiotics in reserve, so they are beginning to use two or three different antibiotics together in combination to fight highly resistant infections. My lab is taking this idea but repurposing it within the chitosan nanoparticle framework to bring a combination of drugs right into the uterus of cows infected with metritis.”
KC Jeong with Zhengxin Ma, a post-doctoral researcher, looking at a nematode, Caenorhabditis elegans, using a microscope.
The goal is to investigate how to amplify the antimicrobial properties of chitosan nanoparticles by coupling them with two other agents used to fight antibiotic resistant bacteria: third generation cephalosporin antibiotics and β-lactamase inhibitors. Cephalosporin antibiotics are one of the best broad-spectrum antibiotics on the market today,