The laboratory conducts basic research in two gastrointestinal parasites: Giardia duodenalis and Trichinella spiralis.
Giardia duodenalis is a common intestinal parasite in humans worldwide that causes giardiosis which is one of the most frequently diagnosed waterborne diseases and is considered a major public health problem particularly in developing countries
The work that we carry out in our research group includes the study of basic aspects of host-pathogen interaction. We are particularly interested in identifying parasite molecules which are expressed and secreted during the interaction of parasite with epithelial cells such as proteases and other virulence factors. Also we have addressed the analysis of the damage caused by these factors at the intestinal epithelium in order to understand at the molecular level the pathogenic mechanisms that occur during experimental giardiasis. These studies will define parasite components that induce epithelial level damage and will allow the design of strategies for the control and prevention of this infection in humans and in animals that potentially can transmit the infection to human.
Another study in our group t is the analysis of the molecular mechanisms involved in the process of encystation of Giardia. In one hand we have studied the inductive phase of encystation in order to identify proteins involved in this phase and on the other we are interested in developing strategies to block the conversion of infective cysts to trophozoites. Particularly we are interested on the identification and characterization of molecules of this parasite involved in signaling pathways and that have differential properties in mammalian counterparts. In this context we have characterized isoforms of the protein kinase C (PKC) and determined their distribution and participation in the inductive stage of encystment. These studies will allow the identification and the development of compounds that interact specifically with selected subdomains of these proteins and thereby to inhibit this process in this parasite.
Unlike current trends in the search for new synthetic compounds, our group is interested in testing the effect of natural products such as garlic compounds Thioalyl on Giardia. Our particular interest has been focused on determining the capacity of allyl-sulphides, of allyl, tiosulfinatos-and allyl cysteine to carry out exchange reactions of type thiol-disulfide with proteins of G. duodenalis, considering that these components may be promising for the treatment of giardiasis. Thus these compounds could be used to control giardiasis preventing the development of resistance in this parasite. Also its production cost may be low when considering its use on a massive scale.
Our group has also approached the study of the mechanisms involved in the induction of resistance to drugs commonly used in the treatment of giardiasis. For this purpose we have obtained resistant G. duodenalis strains and clones to different drugs and these have been used to identified both mechanisms and molecules that are involved, particularly, in the resistance to albendazole. These studies will allow us to define very important processes in the induction of resistance and will contribute to develop a solid platform for the development of other useful methods for the treatment of the giardiasis.
Analysis of the intestinal immune response to Trichinella spiralis in experimental models
Development of vaccination strategies in trichinellosis using stage specific antigens of Trichinella spiralis or petides from these molecules cloned in live attenuated vectors and/or used in conjunction with bacterial adjuvants.
Study of virulence factors of this parasite and its role in the pathogenicity of giardiasis.
Analysis of the inductive phase of encystment in this parasite.
Analysis of in vitro susceptibility of this parasite to different chemotherapeutic agents.
Identification of the mechanisms involved in drug resistance in this parasite.
Parasites of the genus Trichinella are wide spread in nature and these have the ability to infect large members of omnivorous and carnivorous animals, incidental host and humans. Trichinella species display unique and biologically interesting complexity both as parasites and in their interactions with the host cells that they inhabit. Our current understanding indicates that the molecular and cellular dissection of these interactions will provide novel insights on basic biology of both the host and the parasite.
In particular, our research has been directed towards the identification of antigens that trigger both innate and acquired immune responses in different hosts and particularly in experimental models. In these studies we have shown that mast cells participate actively in Trichinella infection and that these cells are activated directly by muscle larvae components such as TSL-1. Upon activation mast cells release important mediators such as histamine MC protease 5, IL-4 and TNF alpha. These immunomodulators may play a role in early immune responses that will contribute to the expulsion of the parasite and thus controlling the infection in the host. Defining the role of mast cells in infections by this parasite offers perspectives for understanding the mechanisms of protection and thus be able to design strategies for the control and prevention of this infection.
Our group is also interested in identifying antigens that induce protective responses against the parasite. In this context we have demonstrated that TSL-1 antigens together with various adjuvants which include lumazine synthase from Brucella sp or cloned epitopes of TSL-1 antigens in attenuated live vectors such as Salmonella enterica ser. Typhimurium were able to induce partial protection in the host against infection. Thus these studies offer a promising platform for the development of vaccines for control of trichinellosis particularly in animals such as pigs that are the major source of infection for humans.
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