Bacterial changes point to new therapies for Legionnaires’ disease
By Caitlin Hayes, Cornell Chronicle
The bacteria Legionella can survive in water systems for years and can cause acute and chronic illness: In 2014-15, it was blamed for at least 12 deaths in the Flint water crisis in Michigan, and as recently as 2023, health officials in Ithaca warned of an outbreak after multiple reported infections and one death.
A new study, published Jan. 23 in the Journal of Bacteriology, elucidates how Legionella – as well as Coxiella burnetii (C. burnetii), which causes Q fever – persist in the environment and in the body, identifying a key enzyme that could be used as a target for treatment.
“We already knew that when these bacteria come out into the environment, they differentiate into intrinsically resistant forms in order to survive,” said Dipak Kathayat, senior author and postdoctoral researcher in the College of Veterinary Medicine. “In our study, we look at what is different between the forms of the cells … and what we found is that the bacteria remodels its envelope, it changes its outer coat.”
When the cells enter water (Legionella) or soil (C. burnetii), the cell envelope becomes hardier, making the bacteria more resistant to antibiotics and, in the case of Legionella, chlorination. This same toughening process occurs in bacterial cells in the human body: When the infections move from acute to chronic, the envelopes change and the diseases become very difficult, or impossible, to treat.
Outbreaks of Legionella, which spread via mist or water vapor and can lead to pneumonia-like symptoms, have occurred throughout the northeastern and midwestern U.S. and are surging worldwide. C. burnetii, spread via livestock and causing the highly contagious Q fever, is classified as a category B bioterrorism agent and presents a threat in farming communities. Both Legionnaires’ disease and Q fever are dangerous and potentially fatal for immunocompromised people; one in 10 people who contract Legionnaires’ disease dies.
Kathayat and his team were able to identify a crucial enzyme, LD-transpeptidase, the bacteria cells need to transform from the rapidly replicating form in a person or animal to the hardy form that allows it to survive in the environment. With LD-transpeptidase as a target, researchers may be able to design better treatment and decontamination protocols.
“We could decontaminate with different chemical agents by targeting the LD-transpeptidase,” Kathayat said. “We also suggest that the chemical agents or drugs that target these enzymes could be utilized for treating chronic infection, too. It can lead to a better, rational therapeutic approach.”
A class of antibiotics that target these enzymes, called carbapenems, is already available, but they haven’t been tested as a treatment for chronic infection of Legionnaires’ disease or Q fever. But Kathayat tested these antibiotics on the more resistant version of Legionella in the lab and found them effective.
“I could see the results of the antibiotic susceptibility results with the naked eye, I could see that the form that’s resistant to antibiotics becomes susceptible to carbapenems,” Kathayat said. “That excites me the most.”
The researchers also suggest that copper, which inactivates LD-transpeptidase, could possibly be used to decontaminate reservoirs.
Co-authors of the study include doctoral student Joee Denis; and undergraduate researchers Yujia Huang ’23, Benjamin Rudoy ’22, Hana Schwarz ’23, and Jacob Szlechter ’24.
The research was supported with funding from the Department of Population Medicine and Diagnostic Sciences and the Cornell Institute of Biotechnology seed grants program.
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