Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families.

Proteolytic enzymes, also known as peptidases, are critical in all living organisms. Peptidases control the cleavage, activation, turnover, and synthesis of proteins and regulate many biochemical and physiological processes. They are also involved in several pathophysiological processes.

Marine gregarine genomes reveal the breadth of apicomplexan diversity with a partially conserved glideosome machinery.

Our current view of the evolutionary history, coding and adaptive capacities of Apicomplexa, protozoan parasites of a wide range of metazoan, is currently strongly biased toward species infecting humans, as data on early diverging apicomplexan lineages infecting invertebrates is extremely limited. Here, we characterized the genome of the marine eugregarine Porospora gigantea, intestinal parasite of Lobsters, remarkable for the macroscopic size of its vegetative feeding forms (trophozoites) and its gliding speed, the fastest so far recorded for Apicomplexa. Two highly syntenic genomes named A and B were assembled.

Genome Sequence and Assessment of Safety and Potential Probiotic Traits of CNCM I-4884.

The probiotic strain CNCM I-4884 exhibits anti- activity in vitro and in vivo in a murine model of giardiasis. The aim of this study was the identification and characterization of the probiotic potential of CNCM I-4884, as well as its safety assessment. This strain was originally classified as based on 16S gene sequence analysis.

Structure-activity relationship and molecular modelling studies of quinazolinedione derivatives MMV665916 as potential antimalarial agent.

A series of new quinazolinedione derivatives have been readily synthesized and evaluated for their in vitro antiplasmodial growth inhibition activity. Most of the compounds inhibited P. falciparum FcB1 strain in the low to medium micromolar concentration.

Age and Infection Impact Canine Gut Microbiota.

is a flagellated protozoan responsible for giardiosis (also called giardiasis in humans), the most prevalent and widespread parasitic infection in humans and mammals worldwide. The intestinal microbiota is highly diverse and any alteration in its composition may impact on the health of the host. While studies on the mouse model of giardiosis described the role of the gut microbiota in host susceptibility to infection by the parasite, little is known about the gut microbiota during natural infections in dogs and particularly in puppies.

Nutrient Acquisition and Attachment Strategies in Basal Lineages: A Tough Nut to Crack in the Evolutionary Puzzle of Apicomplexa.

Apicomplexa are unicellular eukaryotes that parasitise a wide spectrum of invertebrates and vertebrates, including humans. In their hosts, they occupy a variety of niches, from extracellular cavities (intestine, coelom) to epicellular and intracellular locations, depending on the species and/or developmental stages. During their evolution, Apicomplexa thus developed an exceptionally wide range of unique features to reach these diversified parasitic niches and to survive there, at least long enough to ensure their own transmission or that of their progeny.

Programmed Multiple C-H Bond Functionalization of the Privileged 4-hydroxyquinoline Template.

The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C-H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C-H functionalization of a "programmed" 4-hydroxyquinoline.

Integrative taxonomy confirms that Gregarina garnhami and G. acridiorum (Apicomplexa, Gregarinidae), parasites of Schistocerca gregaria and Locusta migratoria (Insecta, Orthoptera), are distinct species.

Orthoptera are infected by about 60 species of gregarines assigned to the genus Gregarina Dufour, 1828. Among these species, Gregarina garnhami Canning, 1956 from Schistocerca gregaria (Forsskål, 1775) was considered by Lipa et al. in 1996 to be synonymous with Gregarina acridiorum (Léger 1893), a parasite of several orthopteran species including Locusta migratoria (Linné, 1758).

Biochemical evidences for M1-, M17- and M18-like aminopeptidases in marine invertebrates from Cuban coastline.

Metallo-aminopeptidases (mAPs) control many physiological processes. They are classified in different families according to structural similarities. Neutral mAPs catalyze the cleavage of neutral amino acids from the N-terminus of proteins or peptide substrates; they need one or two metallic cofactors in their active site.

Aminobenzosuberone derivatives as PfA-M1 inhibitors: Molecular recognition and antiplasmodial evaluation.

Aminobenzosuberone-based PfA-M1 inhibitors were explored as novel antimalarial agents against two different Plasmodium falciparum strains. The 4-phenyl derivative 7c exhibited the most encouraging growth inhibitory activity with IC values of 6.5-11.

Why the -omic future of Apicomplexa should include gregarines.

Gregarines, a polyphyletic group of apicomplexan parasites infecting mostly non-vertebrates hosts, remains poorly known at taxonomic, phylogenetic and genomic levels. However, it represents an essential group for understanding evolutionary history and adaptive capacities of apicomplexan parasites to the remarkable diversity of their hosts. Because they have a mostly extracellular lifestyle, gregarines have developed other cellular developmental forms and host-parasite interactions, compared with their much better studied apicomplexan cousins, intracellular parasites of vertebrates (Hemosporidia, Coccidia, Cryptosporidia).

IgG antibody response against Plasmodium falciparum aminopeptidase 1 antigen in Gabonese children living in Makokou and Franceville.

The search for novel chemical classes of anti-malarial compounds to cope with the current state of chemoresistance of malaria parasites has led to the identification of Plasmodium falciparum aminopeptidase 1 (PfA-M1) as a new therapeutic target. PfA-M1, known to be involved in the hemoglobin digestion cascade which helps to provide most of the amino acids necessary to the parasite's metabolism, is currently considered as a promising target for anti-malarial chemotherapy. However, its immunogenic properties have not yet been tested in the Gabonese population.

Metallopeptidases of Toxoplasma gondii: in silico identification and gene expression.

Metallopeptidases are a family of proteins with domains that remain highly conserved throughout evolution. These hydrolases require divalent metal cation(s) to activate the water molecule in order to carry out their catalytic action on peptide bonds by nucleophilic attack. Metallopeptidases from parasitic protozoa, including Toxoplasma, are investigated because of their crucial role in parasite biology.

Bile Salt Hydrolase Activities: A Novel Target to Screen Anti- Lactobacilli?

is a protozoan parasite responsible for giardiasis, a disease characterized by intestinal malabsorption, diarrhea and abdominal pain in a large number of mammal species. Giardiasis is one of the most common intestinal parasitic diseases in the world and thus a high veterinary, and public health concern. It is well-established that some probiotic bacteria may confer protection against this parasite and and we recently documented the implication of bile-salt hydrolase (BSH)-like activities from strain La1 of as mediators of these effects .

Bile-Salt-Hydrolases from the Probiotic Strain La1 Mediate Anti-giardial Activity and .

(syn. ) is the protozoan parasite responsible for giardiasis, the most common and widely spread intestinal parasitic disease worldwide, affecting both humans and animals. After cysts ingestion (through either contaminated food or water), excysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms.

Discovery of novel non-competitive inhibitors of mammalian neutral M1 aminopeptidase (APN).

Neutral metallo-aminopeptidase (APN) catalyzes the cleavage of neutral and basic amino acids from the N-terminus of protein or peptide substrates. APN expression is dysregulated in inflammatory diseases as well as in several types of cancer. Therefore, inhibitors of APN may be effective against cancer and inflammation.

KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library.

Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P.

Comparative Antibody Responses Against three Antimalarial Vaccine Candidate Antigens from Urban and Rural Exposed Individuals in Gabon.

The analysis of immune responses in diverse malaria endemic regions provides more information to understand the host's immune response to Several plasmodial antigens have been reported as targets of human immunity. PfAMA1 is one of most studied vaccine candidates; PfRH5 and Pf113 are new promising vaccine candidates. The aim of this study was to evaluate humoral response against these three antigens among children of Lastourville (rural area) and Franceville (urban area).