Diversity of Phospholipases A(2) from Bothrops atrox Snake Venom: Adaptive Advantages for Snakes Compromising Treatments for Snakebite Patients

Author(s)

Sousa, Leijiane F. ; Freitas, Amanda P. ; Cardoso, Bruna L. ; Del-Rei, Tiago H. M. ; Mendes, Vanessa A. ; Orefice, Daniele P. ; Rocha, Marisa M. T. ; Prezoto, Benedito C. ; Moura-da-Silva, Ana M.

• Document type: Journal article
• Source: TOXINS; v. 14, n. 8, p. 24-pg., 2022-08-01.

Abstract

The evolution of snake venoms resulted in multigene toxin families that code for structurally similar isoforms eventually harboring distinct functions. PLA(2)s are dominant toxins in viper venoms, and little is known about the impact of their diversity on human envenomings and neutralization by antivenoms. Here, we show the isolation of three distinct PLA(2)s from B. atrox venom. FA1 is a Lys-49 homologue, and FA3 and FA4 are catalytic Asp-49 PLA(2)s. FA1 and FA3 are basic myotoxic proteins, while FA4 is an acid non-myotoxic PLA(2). FA3 was the most potent toxin, inducing higher levels of edema, inflammatory nociception, indirect hemolysis, and anticoagulant activity on human, rat, and chicken plasmas. FA4 presented lower anticoagulant activity, and FA1 had only a slight effect on human and rat plasmas. PLA(2)s presented differential reactivities with antivenoms, with an emphasis on FA3, which was not recognized or neutralized by the antivenoms used in this study. Our findings reveal the functional and antigenic diversity among PLA(2)s from B. atrox venom, highlighting the importance of assessing venom variability for understanding human envenomations and treatment with antivenoms, particularly evident here as the antivenom fails to recognize FA3, the most active multifunctional toxin described. (AU)

• FAPESP's process: 14/13124-2 - Variability in Bothrops atrox snake venom from Western Pará: implications for snake ecology and pathophysiology of envenoming
• Grantee: Leijiane Figueira de Sousa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/50127-5 - Dimensions US-BIOTA São Paulo: scales of biodiversity: integrated studies of snake venom evolution and function across multiple levels of diversity
• Grantee: Inácio de Loiola Meirelles Junqueira de Azevedo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 17/15170-0 - Characterization of mechanisms involved in the hemostatic disturbances induced by Bothrops atrox venoms from three locations of Brazilian Amazon
• Grantee: Leijiane Figueira de Sousa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate