Acanthamoeba spp toxins as virulence factors in infections of the ocular surface.

Principal Investigator:

Fábio Ramos de Souza Carvalho

Awardee:

Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo, SP, Brazil
Field of knowledge:Health Sciences - Collective Health
Support type:Research Awards - Young Investigators Awards
Grant number: 11/51626-1
Duration: July 01, 2012 - June 30, 2016
Associated scholarship(s):12/15603-0 - Acanthamoeba spp toxins as virulence factors in infections of the ocular surface, BP.JP
Abstract
Free-living amoebae of the genus Acanthamoeba are eukaryotlc organisms, aerobic and widely dispersed in nature, which can inhabit aquatic and terrestrial environments. Over the past year, these protozoa have assumed importance in human diseases, including fatal infections and debilitating diseases, primarily involving the nervous system and eye. Epidemiological data about the encephalitis due to Acanthamoeba spp in Brazil are scarce. In addition, clinical cases of ocular infection by Acanthamoeba spp associated with the corneal epithelium (amoebic keratitis), for example, have shown an annual increase. The process of corneal infection by the protozoan occurs in three steps: (1) adhesion of the protozoan on the surface, (2) invasion and destruction of the epithelium and (3) stromal degradation followed by the establishment of the ulcer. At ali stages of infection, the parasite can produce and secrete toxins with different spectra of action in the corneal tissue, inducing cell death, degradation of matrix components and cellular inhibition of wound healing and tissue regeneration. The set of extracellular toxins produced and secreted by Acanthamoeba spp is called secretoma and may consist of proteolytic enzymes and phospholipases of different classes, whose targets and mechanisms of action are still poorly understood. Recently, secretoma of clinicai isolates of Acanthamoeba spp was partially characterized by our research group and the diversity of proteolytic enzymes produced by the protozoan was correlated with the clinicai severity observed in patients. In this research project we intend to isolate and identify the toxins produced by Acanthamoeba spp in order to (i) understand the main mechanisms of pathogenicity of the protozoan in the cell biology of the corneal epithelium and (ii) achieve practical solutions focused in the inhibition of enzymatic activity expressed by trophozoites of Acanthamoeba spp in different stages of infection in the host. We hope to obtain results indicating potential for the development of biotechnological tools aimed at inactivation of proteolytic activity and / or induction of cell death of the protozoa, minimizing the cytotoxic effects caused by icanthamoeba spp on the surface of the cornea, which can provide better quality of life for patients. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PIRES MAFRA, CECILIA SALES; CARRIJO-CARVALHO, LINDA CHRISTIAN; CHUDZINSKI-TAVASSI, ANA MARISA; DE CARVALHO TAGUCHI, FELIPE MARQUES; FORONDA, ANNETTE SILVA; DE SOUZA CARVALHO, FABIO RAMOS; DE FREITAS, DENISE. Antimicrobial Action of Biguanides on the Viability of Acanthamoeba Cysts and Assessment of Cell Toxicity. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 54, n. 9, p. 6363-6372, SEP 2013.
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