Susceptibility of Axenic Amastigotes to the Calpain Inhibitor MDL28170.

Leishmaniasis encompasses a group of neglected diseases caused by flagellated protozoa belonging to the genus, associated with high morbidity and mortality. The search for compounds with anti- activity that exhibit lower toxicity and can overcome the emergence of resistant strains remains a significant goal. In this context, the calpain inhibitor MDL28170 has previously demonstrated deleterious effects against promastigote forms of , which led us to investigate its role on axenic amastigote forms.

Chagas Disease Control-Many Approaches to Prospect.

Chagas disease is an emerging and neglected tropical disease caused by the protozoan parasite estimated to infect 8 to 10 million people worldwide, according to the World Health Organization [...

Development of Echinocandin Resistance in : An Emergent, Widespread, and Opportunistic Fungal Pathogen.

Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant species. Among these species, those belonging to the complex are rare multidrug-resistant (MDR) yeasts that are frequently misidentified but have emerged as significant healthcare-associated pathogens causing invasive infections. The objectives of this study were to investigate the evolutionary pathways of echinocandin resistance in by identifying mutations in the gene and evaluating the impact of resistance on fitness.

Silver(I) and Copper(II) 1,10-Phenanthroline-5,6-dione Complexes as Promising Antivirulence Strategy against : Focus on Gp63 (Leishmanolysin).

Leishmaniasis, caused by protozoa of the genus , encompasses a group of neglected diseases with diverse clinical and epidemiological manifestations that can be fatal if not adequately and promptly managed/treated. The current chemotherapy options for this disease are expensive, require invasive administration and often lead to severe side effects. In this regard, our research group has previously reported the potent anti- activity of two coordination compounds (complexes) derived from 1,10-phenanthroline-5,6-dione (phendione): [Cu(phendione)].

SARS-CoV-2 Post-Infection and Sepsis by : A Fatal Case Report-Focus on Fungal Susceptibility and Potential Virulence Attributes.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the and genera.

The Anti- and Anti- Action of Copper(II) and Silver(I) 1,10-Phenanthroline-5,6-dione Coordination Compounds.

Leishmaniasis is a neglected disease caused by protozoa belonging to the genus. Notably, the search for new, promising and potent anti- compounds remains a major goal due to the inefficacy of the available drugs used nowadays. In the present work, we evaluated the effects of 1,10-phenanthroline-5,6-dione (phendione) coordinated to silver(I), [Ag(phendione)]ClO (Ag-phendione), and copper(II), [Cu(phendione)](ClO)·4HO (Cu-phendione), as potential drugs to be used in the chemotherapy against and .

Differences in Charge Distribution in Leishmanolysin Result in a Reduced Enzymatic Activity.

is a non-pathogenic trypanosomatid isolated from lizards widely used for heterologous protein expression and extensively studied to understand the pathogenic mechanisms of leishmaniasis. The repertoire of leishmanolysin genes was reported to be expanded in genome, but no proteolytic activity was detected. Here, we analyzed leishmanolysin proteins from the genome to the structural levels and evaluated the enzymatic activity of the wild-type and overexpressing mutants of leishmanolysin.

Decoding the antifungal resistance mechanisms in biofilms of emerging, ubiquitous and multidrug-resistant species belonging to the Scedosporium/Lomentospora genera.

Unlabelled: The opportunistic filamentous fungi belonging to the Scedosporium and Lomentospora genera are highly tolerant to all classes of available antifungal drugs. Moreover, the mature biofilm formed by these fungi presents higher antifungal resistance when compared to planktonic cells. Nevertheless, the resistance mechanisms developed by the biofilm lifestyle are not completely elucidated.

Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B.

The necessity of drug combinations to treat leishmaniasis came to the surface mainly because of the toxicity of current treatments and the emergence of resistant strains. The calpain inhibitor MDL28170 has previously shown anti- activity, therefore its use in association with standard drugs could provide a new alternative for the treatment strategy against leishmaniasis. In this study, we analyzed the potential of the combination of MDL28170 and the antileishmanial drug amphotericin B against and .

The Enhanced Expression of Cruzipain-Like Molecules in the Phytoflagellate Recovered From the Invertebrate and Plant Hosts.

is a protozoan parasite that alternates its life cycle between two hosts: an invertebrate vector and the tomato fruit. This phytoflagellate is able to synthesize proteins displaying similarity to the cysteine peptidase named cruzipain, an important virulence factor from , the etiologic agent of Chagas disease. Herein, the growth of in complex medium (BHI) supplemented with natural tomato extract (NTE) resulted in the increased expression of cysteine peptidases, as verified by the hydrolysis of the fluorogenic substrate Z-Phe-Arg-AMC and by gelatin-SDS-PAGE.

Exploring Innovative Leishmaniasis Treatment: Drug Targets from Pre-Clinical to Clinical Findings.

Leishmaniasis is a group of tropical diseases caused by parasitic protozoa belonging to the genus Leishmania. The disease is categorized in cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The conventional treatment is complex and can present high toxicity and therapeutic failures.

Anti-Leishmania braziliensis activity of 1,10-phenanthroline-5,6-dione and its Cu(II) and Ag(I) complexes.

Leishmaniasis, included in the priority list of the WHO, remains as a neglected disease caused by parasites of the Leishmania genus. There is no vaccine available for human leishmaniasis, and the current treatment is based on old drugs that cause serious side effects. Herein, we initially studied the cellular distribution of the virulence factor gp63, the major metallopeptidase, in a virulent strain of Leishmania braziliensis, and then we measured the inhibitory effects of 1,10-phenanthroline-5,6-dione (phendione), and its metal complexes, [Cu(phendione)](ClO).

Analysis of the mechanisms of action of isopentenyl caffeate against Leishmania.

Leishmaniasis is a neglected parasitic disease for which the conventional treatment can be considered inefficient and extremely aggressive, generating several and severe side effects. Therefore, the discovery of new drug candidates is important for the improvement in the quality of life of patients. Previously, we reported the promising results of isopentyl caffeate (ICaf) against Leishmania chagasi (agent of visceral leishmaniasis) and Leishmania amazonensis (agent of cutaneous leishmaniasis) promastigotes, displaying IC of 1.

Repositioning Lopinavir, an HIV Protease Inhibitor, as a Promising Antifungal Drug: Lessons Learned from -In Silico, In Vitro and In Vivo Approaches.

The repurposing strategy was applied herein to evaluate the effects of lopinavir, an aspartic protease inhibitor currently used in the treatment of HIV-infected individuals, on the globally widespread opportunistic human fungal pathogen by using in silico, in vitro and in vivo approaches in order to decipher its targets on fungal cells and its antifungal mechanisms of action. Secreted aspartic proteases (Saps) are the obviously main target of lopinavir. To confirm this hypothesis, molecular docking assays revealed that lopinavir bound to the Sap2 catalytic site of as well as inhibited the Sap hydrolytic activity in a typically dose-dependent manner.

Doxycycline treatment reestablishes renal function of Wistar rats in experimental envenomation with Bothrops jararacussu venom.

Acute kidney injury is one of the main complications of ophidian accidents and the leading cause of death in patients who survive the initial damage effects of venom. The hypothesis proposed in this investigation is that the pharmacological repositioning of doxycycline (doxy) attenuates renal injury provoked by Bothrops jararacussu (Bj) venom. Male Wistar rats were subjected or not (control) to experimental envenomation with Bj venom (3.

Insights into the Multi-Azole Resistance Profile in Species Complex.

The complex (, , and var. ) is composed of emerging, opportunistic human fungal pathogens able to cause invasive infections with high rates of clinical treatment failure. This fungal complex typically demonstrates resistance to first-line antifungals, including fluconazole.

β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity.

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings.

Secreted aspartyl peptidases by the emerging, opportunistic and multidrug-resistant fungal pathogens comprising the Candida haemulonii complex.

The opportunistic pathogens comprising the Candida haemulonii complex (C. haemulonii, C. duobushaemulonii and C.

Unmasking the Amphotericin B Resistance Mechanisms in Species Complex.

The polyene amphotericin B (AMB) exerts a powerful and broad antifungal activity. AMB acts by (i) binding to ergosterol, leading to pore formation at the fungal plasma membrane with subsequent ion leakage, and (ii) inducing the intracellular accumulation of reactive oxygen species (ROS). Herein, we have deciphered the AMB resistance mechanisms in clinical isolates of complex (, , var.

Surface, adhesiveness and virulence aspects of Candida haemulonii species complex.

The emerging opportunistic pathogens comprising the Candida haemulonii complex (C. haemulonii [Ch], C. duobushaemulonii [Cd] and C.