Butantan finds antibiotic potential in Amazonian frog venom

Research by the Butantan Institute identifies antimicrobial peptides in cane toad venom and paves the way against resistant bacteria

O identified peptides with antimicrobial properties in the venom of the Amazon cane toad (Rhaebo fell). The work was coordinated by biomedical scientist Daniel Pimenta, researcher at the Butantan Ecology and Evolution Laboratory. The discovery was published in the scientific journal Toxicon. Researchers from the Escola Paulista de Medicina da Unifesp and the Center for Studies in Biomolecules Applied to Health at Fiocruz, in Rondônia, participated in the study.

Proteomic analysis mapped the proteins present in the secretion of Rhaebo fell. The protein fragments demonstrated possible antimicrobial properties through structural and functional analyzes carried out in silico — computational tools that help predict or understand the biological function of molecules.

“In a context of antimicrobial resistance, the search for new antibiotic compounds in nature is an important strategy for the future development of drugs capable of combating resistant bacteria”said Daniel Pimenta.

The venom stored in glands located in the frogs’ skin works as a “shield”. The secretion protects the animal against predators and also against possible pathogens present in the environment, such as viruses, bacteria and fungi. The skin secretion of amphibians is composed of elements with diverse biological effects, including antibacterial and antiviral.

The analysis unexpectedly revealed the presence of BASP1, a protein that had not been identified in anuran venoms until now. The anuran order includes toads, frogs and tree frogs. BASP1 is commonly found in the nervous systems of humans and animals.

Scientists hypothesize that the protein may play a role in skin gland contraction and regeneration. This gland undergoes a natural inflammatory process when the venom is secreted, but this function still needs to be confirmed by additional studies.

The researchers also identified proteins related to muscle contraction, oxidative stress and cane toad immunity. The venom is made up of a complex mixture of hundreds of molecules.

The research was developed at the Biochemistry Laboratory of the Butantan Institute. Scientists performed a proteomic analysis to separate and identify only the proteins within this complex mixture. The first challenge was transforming the viscous, yellowish secretion into a solution — that is, a homogeneous mixture —, a form suitable for laboratory equipment to process the sample.

The venom components were separated by liquid chromatography. The resulting fractions were inserted into the mass spectrometer, a device that analyzes each molecule of the venom individually. The equipment provides a “photograph” which helps to identify the substances present in the sample.

“In addition to having contributed to the knowledge about this Amazonian species, which is very little studied, and having identified peptides with antibiotic potential, we observed that its venom has many similarities with that of the cane toad from southeastern Brazil [Rhinella icterica] and with that of the species introduced in Australia [Rhinella marina]declared Daniel Pimenta.

The frogs known as “cururu” They are native to South America. Some species were introduced to Asian countries and the United States in an attempt to control agricultural pests.

PREVIOUS DISCOVERY

In a previous study with the Rhaebo fellconducted in 2011 in collaboration with scientific researcher Carlos Jared, director of the Structural and Functional Biology Laboratory at Butantan, researchers discovered that the species is capable of ejecting venom — which until that moment was considered a myth.

The work, published in Amphibia-Reptiliashowed that the Amazon frog releases venom from glands located behind its eyes when it feels threatened. It was the first time this type of behavior was described in scientific literature.

“The results demonstrate how these studies, in addition to searching for therapeutic molecules, can also help provide answers about the animal’s basic biology — who it is, what it secretes, how it defends itself”said Daniel Pimenta.

The research was funded by Capes (Coordination for the Improvement of Higher Education Personnel) and by (São Paulo State Research Support Foundation). The venom samples were provided by the Center for Studies on Biomolecules Applied to Health at located in Rondônia.


With information from