Insights into the Role of Proteolytic and Adhesive Domains of Snake Venom Metalloproteinases from <i>Bothrops</i> spp. in the Control of <i>Toxoplasma gondii</i> Infection
Samuel C. Teixeira,
Thales A. M. Fernandes,
Guilherme de Souza,
Luana C. Luz,
Marina Paschoalino,
Joed P. de L. Junior,
Alessandra M. Rosini,
Aryani F. F. Martínez,
Vitor de Freitas,
Daiana S. Lopes,
Patrícia B. Clissa,
Vinícius C. de Souza,
Milton Y. Nishiyama-Jr.,
Bellisa F. Barbosa,
Eloisa A. V. Ferro,
Veridiana de M. R. Ávila
Affiliations
Samuel C. Teixeira
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Thales A. M. Fernandes
Laboratory of Applied Toxinology, Butantan Institute, São Paulo 05503-900, SP, Brazil
Guilherme de Souza
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Luana C. Luz
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Marina Paschoalino
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Joed P. de L. Junior
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Alessandra M. Rosini
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Aryani F. F. Martínez
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Vitor de Freitas
Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Daiana S. Lopes
Institute Multidisciplinary in Health, Universidade Federal da Bahia (UFBA), Vitória da Conquista 45029-094, BA, Brazil
Patrícia B. Clissa
Laboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, SP, Brazil
Vinícius C. de Souza
Laboratory of Applied Toxinology, Butantan Institute, São Paulo 05503-900, SP, Brazil
Milton Y. Nishiyama-Jr.
Laboratory of Applied Toxinology, Butantan Institute, São Paulo 05503-900, SP, Brazil
Bellisa F. Barbosa
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Eloisa A. V. Ferro
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Veridiana de M. R. Ávila
Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberlândia, Uberlândia 38405-318, MG, Brazil
Toxoplasmosis is an alarming public health problem that affects more than one-third of the world’s population. In our work, we investigated the antiparasitic effects of catalytically active [BpMP-I and Jararhagin (Jar)] and catalytically inactive [Jararhagin-C (Jar-C)] snake venom metalloproteinases (SVMPs) in human HeLa cells. These toxins impaired the parasite invasion and intracellular growth, and modulated IL-6, IL-8, and MIF cytokines that control the cell susceptibility and response against T. gondii. Furthermore, we verified that the antiprotozoal activities are not restricted to the presence of the proteolytic domain, and the adhesive domains participate in the control of T. gondii infection. Also, by analyzing the structures of Jar and Jar-C through molecular modeling and dynamics, we observed that the adhesive domains in Jar-C are more exposed due to the absence of the proteolytic domain, which could favor the interaction with different targets. Our investigation on the role of SVMP domains in combating T. gondii infection highlights their potential application as biotechnological tools for creating more effective treatments for toxoplasmosis.
