Inhibitory Potential of Prodomain of Plasmodium falciparum Protease Serine Repeat Antigen 5 for Asexual Blood Stages of Parasite

Plasmodium falciparum serine repeat antigen 5 (SERA5) is a target for both drug and vaccine intervention against malaria. SERA5 is secreted in the parasitophorous vacuole where it is proteolytically processed before schizont rupture. Among the processed products is a 50.8-kDa central domain of the protease, which possesses chymotrypsin-like activity and consists of a 28.9-kDa catalytic domain with a 21.9-kDa N-terminal prodomain, which remain attached together. Because SERA5 has been implicated in merozoite egress from host erythrocytes, the effect of the prodomain and a heptapeptide derived from its C-terminus spanning from D560 to F566 (DNSDNMF) on parasite growth was studied. When E. coli-expressed prodomain was incubated with parasite culture, a significant delay in transition from schizont to ring stages was observed up to nanomolar concentrations. The peptide, DNSDNMF also showed similar effects but at nearly 1000-fold higher concentrations. The peptide was also found to interact with the catalytic domain. These data demonstrate the crucial role of SERA5 prodomain for the egress process. Given the inhibitory potential of the prodomain for the parasite, we suggest that peptidomimetic inhibitors based on SERA5 prodomain sequences can be developed as future therapeutics against malaria

Cryptosporidium pathogenicity and virulence

Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence

Cryptosporidium

Cryptosporidium sp. infects the gastrointestinal tract of a wide range of vertebrates, including domestic and livestock animals as well as humans. Cryptosporidiosis of neonatal farm ruminants causes considerable economic losses as the disease is commonly associated with intense diarrhea leading to an impaired growth, a decreased performance and production, and often animal death. The highly infective oocyst stage is excreted with the feces and disseminated into the environment, contaminating water and food. Neonatal calves are a major reservoir of the zoonotic C. parvum, which causes, in addition to the anthroponotic C. hominis, human cryptosporidiosis and is of considerable public health concern. Currently, no vaccine or efficient drug is available against the disease. From a veterinarian economical point of view, C. parvum is the most important species among the 30 recognized species infecting bovines, lamb, goats, pigs, horses, and dogs worldwide. After the discovery of C. parvum by Tyzzer in the year 1912, the taxon Cryptosporidium has been classified into coccidia. However, recent findings on the Cryptosporidium life cycle and molecular phylogenetic evidence resulted in the reclassification of Cryptosporidium into the gregarines. This novel placement appreciates previously underestimated and/or neglected features of Cryptosporidium that are common to gregarines such as a low host specificity and/or the possibility to survive without a host.Fil: Tomazic, Mariela Luján. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Garro, Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Schnittger, Leonhard. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Universidad de Morón; Argentin