Some antidepressants could provide treatment for several infectious diseases

Some antidepressants could provide treatment for several infectious diseases

According to research from the Virginia Commonwealth University School of Medicine and collaborators at other institutions, some antidepressants could potentially be used to treat a large number of illnesses caused by living bacteria. inside cells.

Research published in the print edition of April newspaper Alliance of Life Sciences, shows that antidepressants called FIASMA, including desipramine, amitriptyline and nortriptyline, stop growth or suppress four different intracellular bacterial pathogens in animal and tissue cultures.

"Antibiotic options for diseases caused by intracellular bacteria are limited because many of these drugs can not penetrate the membranes of our cells – essentially, the bacteria are protected," said Jason Carlyon, Ph.D. ., director of the study and professor at the VCU department. of microbiology and immunology.

Tetracycline antibiotics are most often prescribed to treat intracellular bacterial infections as they can cross cell membranes to reach microbes. However, tetracyclines can cause allergic reactions in some patients and doctors advise against their use by pregnant women and children because of unwanted side effects. In addition, antibiotic resistance in some intracellular bacteria has been reported.

"It would be very beneficial to have a clbad of drugs to treat such diseases in patients for whom tetracyclines are contraindicated," Carlyon said. "These medications could be an alternative to antibiotics or even used in combination with them as adjunctive treatment for the treatment of infections that usually require prolonged antibiotic treatment, such as those caused by Chlamydia pneumoniae and Coxiella burnetti. "

The team of researchers at VCU, the Indiana University Medical Center, the University of Nebraska Medical Center, the University of Arkansas for Medical Sciences and the University of Florida at the University of South, including Carlyon and lead author Chelsea Cockburn, holds a master's degree in PhD. candidates, are the first to study the mechanisms by which FIASMAs target in detail several intracellular bacteria.

Scientists have tested the susceptibility to FIASMA of four bacterial species responsible for human granulocytic anaplasmosis, a tick-borne disease that attacks white blood cells called neutrophils and can be fatal for immunocompromised individuals; Q fever, a debilitating pneumonic disease; and two chlamydia infections.

FIASMA ultimately disrupts how cholesterol, a key nutrient used by many intracellular pathogens, circulates in cells to alter bacteria's access to lipid. Researchers first demonstrated the efficacy of FIASMA treatment by stopping anaplasmosis in mice and tissue cultures. Next, they extended their observations to demonstrate that treatment with FIASMA had killed the Q fever agent, Coxiella burnetii, and partially inhibited Chlamydia infections in cell culture.

"Since FIASMA has an influence on the trafficking of cholesterol in cells and cholesterol plays a role in many aspects of our biology, they have been used to treat a large number of diseases and conditions," said Carlyon.

He added that the effect of FIASMAs on intracellular cholesterol ultimately circumvents the need to target the bacteria directly.

"What's so exciting about this study is that the clbad of drugs we've been evaluating is targeting an enzyme in our cholesterol-regulating cells, not bacteria," Carlyon said. "I do not think pathogens can develop resistance to this treatment because it targets a host path that they badly need to grow and survive inside the body."

Rebecca Martin, Ph.D., and Daniel Conrad, Ph.D. (VCU), Charles Chalfant, Ph.D. (University of South Florida), Daniel Voth, Ph.D. (University of Arkansas for medical sciences), Elizabeth Rucks, Ph.D. (Medical Center of the University of Nebraska) and Stacey Gilk, Ph.D. (Indiana University School of Medicine).

The research was funded by grants from the National Institute of Allergy and Infectious Diseases of the NIH, including 1R01 AI139072, 2R01 AI072683, 5R01 AI018697, 1R01 AI139176, 1R21 AI127931 and 1R21 AI121786 and National Institute General Practice NIH (1P20) GM103625).

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About VCU and VCU Health

Virginia Commonwealth University is a large urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU welcomes more than 31,000 students in 217 degree and certificate programs in arts, sciences and humanities. Thirty-eight programs are unique in Virginia, many of them straddling the disciplines of the 11 schools and three VCU colleges. The VCU Health brand represents the University VCU Health Sciences programs, the VCU Mbadey Cancer Center and the VCU Health System, which includes the VCU Medical Center (the only Academic Medical Center and Level I Trauma Center in the region), the Community Memorial Hospital and the Children's Hospital. from Richmond at VCU, MCV Physicians and Virginia Premier Health Plan. For more, please visit http: // www.lived.Edu and vcuhealth.org.

This story was published on: 2019-05-31. To contact the author, please use the contact information in the article.

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