A study supported by São Paulo State Research Support Foundation (Fapesp) investigates a molecule developed in the laboratory that has shown effectiveness against candidiasis, an infection. The compound, derived from a peptide naturally produced in the human body (kiotorphine) and conjugated to the medicine ibuprofen, had a strong antifungal action when eradicating strains of several species of the genus Candida, including the most resistant to antimicrobials.
In the analysis, researchers at the Federal University of São Paulo (Unifesp) proved that the derivative, generally used for its analgesic and anti-inflammatory powers, inhibited the formation of organized structures of encapsulated microorganisms.
Called biofilm, this structure produces a series of other molecules that shield colonies of fungi, making it very difficult to destroy them by other antimicrobials available on the market.
“In addition to the discovery that the kiotorphine derivative is a potent antifungal and antibiofilm, another interesting feature of this compound is the fact that it is able to overcome the blood-brain barrier, which also allows it to act on infections in the brain. Thus, the recent findings can be considered a starting point for the design of drugs that can access the central nervous system ”, Fapesp Agency Katia Conceição, researcher at the Peptide Biochemistry laboratory at Unifesp, on the São José dos Campos campus, and coordinator of the research published in the magazine Fungal Biology.
The researcher points out that, in patients with low immunity, a mild fungal infection circulating in the blood can lead to more serious problems. “There has been an increase in resistance to antimicrobials and also in the incidence of fungal infections that affect not only the skin and mucous membranes, but also the central nervous system. Therefore, having an antifungal that inhibits and eradicates biofilms and that can reach the central nervous system is extremely important ”, he stresses.
The action of the fungus on brain regions was evaluated last year in a study coordinated by another group of researchers, whose article was published in the journal Nature Communications. “It was discovered in tests carried out on mice that Candida is also capable of overcoming the blood-brain barrier and reaching the brain, forming inflammatory structures called“ granuloma-like ”which, in turn, share characteristics with beta-amyloid plaques found in the disease Alzheimer’s disease ”, says Conceição.
In the study carried out at Unifesp, the group of researchers tested six kiotorphine derivatives for antimicrobial and antibiofilm activity in eight strains of the genus Candida, including clinics.
“Of the six molecules derived from the peptide, the ibuprofen-conjugated version was the most efficient in inhibiting and eradicating the formation of biofilms in strains of different species of Candida”, He says.
The effect was proven in samples containing colonies of Candida albicans, Candida krusei, Candida dubliniensis, Candida glabrata, Candida lusitaniae, Candida novergensis, Candida parapsilosis and Candida tropicalis.
Kyotorphine is an endogenous peptide that was isolated from the brain of cattle in the 1970s and, later, also from other species, including man. The molecule, initially studied for its analgesic effects, also acts as an antimicrobial, anti-inflammatory and neuroprotective.
“The problem is that the endogenous peptide only showed analgesic activity when injected directly into the brain. For this reason, a consortium of Portuguese, German and Spanish researchers designed molecules derived from the peptide that could cross the blood-brain barrier, reaching the brain when administered intravenously, for example, ”says Conceição.
The group of Brazilian researchers obtained permission to study the six patented derivatives. “That was when we discovered the antifungal and antibiofilm activity of the derivatives, the result of the work of the biotechnology master student Vitor Martins de Andrade. It is also important to highlight the increased survival in vivo of organisms infected with Candida and treated with one of the derivatives ”, he emphasizes.
“We intend in the future to assess whether the derivatives also inhibit the formation of granuloma-like structures and, eventually, beta-amyloid plaques, characteristics of diseases such as Alzheimer’s and Parkinson’s and related to symptoms such as memory loss. Maybe in the future it will be possible to develop drugs based on these molecules for application against neurodegenerative diseases ”, he concludes.
The article (in English) can be read at https://www.sciencedirect.com/science/article/pii/S1878614619301709.