Boa gamma PLI from Boa constrictor Blood is a Broad-Spectrum Inhibitor of Venom PLA(2) Pathophysiological Actions

Author(s)

Rodrigues, Caroline Fabri Bittencourt ^{[1, 2, 3, 4]} ; Zdenek, Christina N. ^[3] ; Serino-Silva, Caroline ^{[1, 2, 4]} ; de Morais-Zani, Karen ^{[1, 2, 4]} ; Grego, Kathleen Fernandes ^[2] ; Benard-Valle, Melisa ^[5] ; Neri-Castro, Edgar ^[5] ; Alagon, Alejandro ^[5] ; Tanaka-Azevedo, Anita Mitico ^{[1, 2, 4]} ; Fry, Bryan Grieg ^[3]

Affiliation

^[1] Inst Butantan, Sao Paulo - Brazil

^[2] Inst Butantan, Lab Herpetol, Sao Paulo - Brazil

^[3] Univ Queensland, Sch Biol Sci, Venom Evolut Lab, St Lucia, Qld 4072 - Australia

^[4] Univ Sao Paulo, IPT, Programa Posgrad Interunidades Biotecnol, Sao Paulo - Brazil

^[5] Univ Nacl Autonoma Mexico, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos - Mexico

• Document type: Journal article
• Source: Journal of Chemical Ecology; v. 47, n. 10-11, p. 907-914, NOV 2021.
• Web of Science Citations: 1

Abstract

The use of venom in predation exerts a corresponding selection pressure for the evolution of venom resistance. One of the mechanisms related to venom resistance in animals (predators or prey of snakes) is the presence of molecules in the blood that can bind venom toxins, and inhibit their pharmacological effects. One such toxin type are venom phospholipase A(2)s (PLA(2)s), which have diverse effects including anticoagulant, myotoxic, and neurotoxic activities. Boa gamma PLI isolated from the blood of Boa constrictor has been previously shown to inhibit venom PLA(2)s that induced myotoxic and edematogenic activities. Recently, in addition to its previously described and very potent neurotoxic effect, the venoms of American coral snakes (Micrurus species) have been shown to have anticoagulant activity via PLA(2) toxins. As coral snakes eat other snakes as a major part of their diet, neonate Boas could be susceptible to predation by this sympatric species. Thus, this work aimed to ascertain if Boa gamma PLI provided a protective effect against the anticoagulant toxicity of venom from the model species Micrurus laticollaris in addition to its ability shown previously against other toxin types. Using a STA R Max coagulation analyser robot to measure the effect upon clotting time, and TEG5000 thromboelastographers to measure the effect upon clot strength, we evaluated the ability of Boa gamma PLI to inhibit M. laticollaris venom. Our results indicate that Boa gamma PLI is efficient at inhibiting the M. laticollaris anticoagulant effect, reducing the time of coagulation (restoring them closer to non-venom control values) and increasing the clot strength (restoring them closer to non-venom control values). These findings demonstrate that endogenous PLA(2) inhibitors in the blood of non-venomous snakes are multi-functional and provide broad resistance against a myriad of venom PLA(2)-driven toxic effects including coagulotoxicity, myotoxicity, and neurotoxicity. This novel form of resistance could be evidence of selective pressures caused by predation from venomous snakes and stresses the need for field-based research aimed to expand our understanding of the evolutionary dynamics of such chemical arms race. (AU)

• FAPESP's process: 18/25786-0 - Phospholipase A2 inhibitors (PLIs) present in venomous and non-venomous snake plasmas and evaluation of the neutralizing activity of these inhibitors on the phospholipase A2 (PLA2) activities of snake venoms
• Grantee: Anita Mitico Tanaka-Azevedo
• Support Opportunities: Regular Research Grants