Researchers from the Virginia Commonwealth University (VCU) School of Medicine and collaborators at other institutions, have recently identified a potential of certain antidepressants drugs called FIASMAs, including desipramine, amitriptyline, and nortriptyline to help treat a wide range of infectious diseases.
Findings from their research showed that FIASMAs are capable of preventing the growth or outright killing of at least four different kinds of intracellular bacterial pathogens found in animal models and tissue cell culture.
Jason Carlyon, a professor from VCU's Microbiology and Immunology Department and lead investigator of the study explained that antibiotic options for diseases caused by intracellular bacteria are limited because many of these drugs cannot penetrate the human cell membranes, as the bacteria are protected.
He noted that infections caused by intracellular bacteria are usually treated using tetracycline. These antibiotics are capable of penetrating cell membranes and attacking the microbes directly.
However, not all patients can receive tetracycline treatment since it can cause some allergic reactions. The drug can also result in adverse side effects in children and pregnant women.
Studies have also identified cases of antibiotic resistance related to intracellular bacterial infections.
Carlyon highlighted the need for a new class of drugs that can treat patients who are not able to receive tetracycline therapy. Such medications can be used either as an alternative to antibiotics, or even as a partner treatment to help augment the impact of antibiotics.
He added that these drugs could be used for infections that require prolonged antibiotic therapies such as those caused by Coxiella burnetti and Chlamydia pneumoniae bacteria.
The team of researchers from VCU, Indiana University Medical Center, University of Nebraska Medical Center, University of Arkansas for Medical Sciences, and the University of South Florida, including Carlyon and lead author Chelsea Cockburn, are the first to investigate the mechanisms by which FIASMAs target multiple intracellular bacteria in detail.
In establishing the link between the aantidepressants and the multiple infectious diseases, the researchers tested the impact of FIASMA on four species of bacteria:
Human granulocytic anaplasmosis – A tick-borne infection that targets the body's white blood cells known as neutrophils.
Q fever -A disease caused by the Coxiella burnetii bacteria and known to transfer from animals to humans, and two kinds of chlamydia infections.
Carlyon and his colleagues observed how FIASMAs can affect cholesterol, an important nutrient used by intracellular pathogens, traffics inside cells to disrupt the access of bacterial to certain lipids. They also saw how such antidepressants can prevent anaplasmosis in both mice and tissue culture samples.
The researchers then tested FIASMA treatment on Coxiella burnetii, a primary agent of Q fever infection, and found how the antidepressants ultimately killed the microbe. The medication also partially inhibited the spread of chlamydial infections in cell culture.
Carlyon explained that since FIASMAs can disrupt the trafficking of cholesterol in cells and cholesterol plays a key role in different facets of human biology, the antidepressants have been used to address a wide range of medical conditions and diseases.
He pointed out that FIASMAs can target intracellular cholesterol, which removes the need for treatments to directly attack bacteria.
The class of drugs that the researchers evaluated were able to target an enzyme in cells known to regulate cholesterol and not the bacterial itself.
The team does not see the pathogens being able to develop some form of resistance to FIASMAs since the treatment targets a pathway that the microbes depend on to survive while inside their host's body.
The findings of the multi-organisational study are featured in the journal sciencedaily
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