As large blooms of toxic blue-green algae have become an annual phenomenon in Florida’s freshwater lakes and rivers, as well as other places worldwide, University of Florida researchers have identified a new method to control its growth.
Pollution and warm water temperatures during the summer months create a favorable environment for algae growth. The blue-green algae, also known as cyanobacteria, threatens drinking water supply, fish and wildlife, agriculture, tourism and human health.
Yousong Ding, Ph.D., an associate professor of medicinal chemistry in the UF College of Pharmacy, is exploring new cellular targets for controlling undesirable microbial growth, which are broadly related to drug-resistant microbial infections and toxic cyanobacteria blooms. In a study published in the American Chemical Society’s journal Chemical Biology, Ding’s research team identified the enzyme dihydroxyacid dehydratase, or DHAD, as a target for inhibiting microbial growth.
“We found a way to essentially starve the cyanobacteria of an important nutrient essential for their growth,” Ding said. “If we can control cyanobacteria bloom development, then we can regain our ability to keep these harmful algae out of Florida’s freshwater lakes and rivers.”
DHAD enzymes are used by microbes as well as plants to produce branched-chain amino acids, or BCAAs. All lifeforms require BCAAs to grow and survive, and cyanobacteria have to make BCAAs on their own. Ding’s research team used chemicals to block the function of DHAD enzymes, which in turn prevented the production of BCAAs and eliminated cyanobacteria growth.
BCAAs are essential to humans and animals. However, humans and animals do not have the needed enzymes, including DHADs, to produce BCAAs on their own. Instead, the BCAAs must be acquired through diets by eating plants, fruits and meats.
“Since humans and animals do not have the DHAD enzyme to make BCAAs, we can use inhibitors to target only cyanobacteria blooms in lakes or rivers without harming people or fish,” Ding said.
DHAD has applications beyond controlling algae growth. As infectious microbes also use DHADs to produce BCAAs for growth, survival and infections, UF researchers believe the enzymes are a new target to develop novel types of antimicrobials to address the drug resistance crisis. Antibiotic resistance occurs when bacteria evolve in response to medications and become resistant to treatments. The Centers for Disease Control and Prevention reports at least 2.8 million Americans are infected with antibiotic-resistant bacteria or fungi annually.
If pathogen growth can be controlled, similar to cyanobacteria, then Ding is optimistic that new medicines can be developed to target microbial infections.
“We have largely lost the ability to control damaging microbial growth, and we see it in the antibiotic resistance and algae problems in Florida,” Ding said. “This new finding offers an encouraging new strategy to selectively inhibit the DHAD enzyme and ultimately address some of society’s biggest environmental and medical challenges.”
The study “Cyanobacterial Dihydroxyacid Dehydratases Are a Promising Growth Inhibition Target,” was published online July 29, and it was selected as the cover story for the upcoming print edition of ACS Chemical Biology.