Generation and characterization of a monoclonal antibody Fab fragment targeting PBP2a in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens associated with nosocomial and community infections that are difficult to treat owing to its resistance to all β-lactams and other classes of antibiotics. Reports of MRSA demonstrate the pathogen relevance and urgency for developing innovative diagnostic and treatment strategies against this microorganism. In this context, monoclonal antibodies (mAbs) represent a powerful tool for such purposes.

Epoxy-a-lapachone in nanosystem: a prototype drug for leishmaniasis assessed in the binomial BALB/c - Leishmania (Leishmania) amazonensis.

This perspective presents and supports arguments for a new formulation of epoxy-α-lapachone loaded microemulsion (ELAP-ME), a nanosystem, as a prototype drug for the treatment of leishmaniasis. The benefits of ELAP as a multitarget compound, with properties that affect key physiological pathways of Leishmania spp. are discussed.

Efficacy of the treatment using a microemulsion loaded with epoxy-α-lapachone in combination with meglumine antimoniate against murine infection by Leishmania (Leishmania) amazonensis.

Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients.

Degron Pathways and Leishmaniasis: Debating Potential Roles of spp. Proteases Activity on Guiding Hosts Immune Response and Their Relevance to the Development of Vaccines.

Degrons are short peptide sequences that signalize target sites for protein degradation by proteases. Herein, we bring forth the discussion on degrons present in proteins related to the immune system of that are potential targets for cysteine and serine proteases of spp. and their possible roles on host immune regulation by parasites.

Assessing nystatin cream treatment efficacy against Leishmania (L.) amazonensis infection in BALB/c model.

The current scenario for cutaneous leishmaniasis treatment includes the use of first and second-choice drugs, both therapeutic strategies presenting several adverse effects and being related to an increment of treatment-refractory parasite strains. These facts encourage the search for new treatment approaches, including repositioning drugs, such as nystatin. Although in vitro assays show that this polyene macrolide compound has leishmanicidal activity, no in vivo evidence for a similar activity has been shown so far for the commercial nystatin cream formulation.

A New Strategy for Mapping Epitopes of LACK and PEPCK Proteins of Specific for Major Histocompatibility Complex Class I.

Leishmaniasis represents a complex of diseases with a broad clinical spectrum and epidemiological diversity, considered a major public health problem. Although there is treatment, there are still no vaccines for cutaneous leishmaniasis. Because spp.

Development of a microemulsion loaded with epoxy-α-lapachone against Leishmania (Leishmania) amazonensis murine infection.

Epoxy-α-lapachone (ELAP), an oxirane-functionalized molecule synthesized from naturally occurring lapachol, has shown promising activity against murine infection with Leishmania (Leishmania) amazonensis. Herein, we report the successful development of oil-in-water-type (o/w) microemulsions (ME) loaded with ELAP (ELAP-ME) using Capmul MCM, Labrasol, and PEG 400. Stability studies revealed that ELAP-ME (100 µg/mL of ELAP), which was comprised of globule size smaller than 120.

Epoxy-α-lapachone (2,2-Dimethyl-3,4-dihydro-spiro[2H-naphtho[2,3-b]pyran-10,2'-oxirane]-5(10H)-one): a promising molecule to control infections caused by protozoan parasites.

Natural products and their derivatives have been sources of search and research for new drugs for the treatment of neglected diseases. Naphthoquinones, a special group of quinones, are products of natural metabolites with a wide spectrum of biological activities and represent a group of interesting molecules for new therapeutic propositions. Among these compounds, lapachol stands out as a molecule from the heartwood of Tabebuia sp.

Novel Insights Into Fitness Guided by Temperature Changes Along With Its Subtilisins and Oligopeptidase B.

Proteases are virulence factors with a recognized impact on the spp. life cycle. This study considers a set of analyses measuring phenotypic factors of clinical isolates as promastigotes growth curves, murine peritoneal macrophages infection, inflammatory mediators production, and serine proteases gene expression (subtilisin 13: S13, subtilisin 28: S28, oligopeptidase B: OPB) assessing these isolates' fitness on conditions.

SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites.

(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analyzed the recruitment of hemoglobin (Hb) and other metabolites (hemin and protoporphyrin IX-PpIX) by SARS-Cov2 proteins using different approaches.

Combining Well-Tempered Metadynamics Simulation and SPR Assays to Characterize the Binding Mechanism of the Universal T-Lymphocyte Tetanus Toxin Epitope TT830-843.

Peptide TT830-843 from the tetanus toxin is a universal T-cell epitope. It helps in vaccination and induces T-cell activation. However, the fine molecular interaction between this antigen and the major histocompatibility complex (MHC) remains unknown.

Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony.

Glucantime (Sb) is the first-line treatment against American Tegumentary Leishmaniasis. Resistance cases to this drug have been reported and related to host characteristics and parasite phenotypes. In this study, 12 Leishmania (Viannia) braziliensis isolates from patients that presented clinical cure (Responders-R) and relapse or therapeutic failure (Non-responders-NR) after treatment with antimony, were analyzed.

In Silico Insights into the Mechanism of Action of Epoxy-α-Lapachone and Epoxymethyl-Lawsone in spp.

Epoxy-α-lapachone (Lap) and Epoxymethyl-lawsone (Law) are oxiranes derived from Lapachol and have been shown to be promising drugs for Leishmaniases treatment. Although, it is known the action spectrum of both compounds affect the spp. multiplication, there are gaps in the molecular binding details of target enzymes related to the parasite's physiology.

Detection of Antibodies against Hepatitis A Virus (HAV) by a Surface Plasmon Resonance (SPR) Biosensor: A New Diagnosis Tool Based on the Major HAV Capsid Protein VP1 (SPR-HAVP1).

Hepatitis A (HA) is an acute human infectious disease caused by a positive single-stranded RNA virus (HAV). It is mainly acquired through the fecal-oral route and is primarily spread by contact between people and exposure to contaminated water and food. Recently, large outbreaks of HA have been reported by low and moderate endemicity countries, emphasizing its importance in public health and the need for rapid and large-scale diagnostic tests to support public health decisions on HA.

Axenic amastigotes of Leishmania species as a suitable model for in vitro studies.

Leishmania spp. are etiological agents of infection diseases, which in some cases can be fatal. The main forms of their biological cycle, promastigotes and amastigotes, can be maintained in vitro.

Insights into the proteomic profile and gene expression of Lutzomyia longipalpis-derived Lulo cell line.

Background: Lutzomyia longipalpis-derived cell line (Lulo) has been suggested as a model for studies of interaction between sandflies and Leishmania.

Objectives: Here, we present data of proteomic and gene expression analyses of Lulo cell related to interactions with Leishmania (Viannia) braziliensis.

Methods: Lulo cell protein extracts were analysed through a combination of two-dimensional gel electrophoresis and mass spectrometry and resulting spots were further investigated in silico to identify proteins using Mascot search and, afterwards, resulting sequences were applied for analysis with VectorBase.

Detection of Metalloproteases and Cysteine Proteases RNA Transcripts of in Ear Edge Skin of Naturally Infected Dogs.

spp. proteases have been proposed as virulence factors contributing to adaptive success these parasites to the mammalian hosts. Since these enzymes are poorly studied in naturally infected dogs, this work aims to show the differences in metalloprotease and cysteine proteases gene expression in ear edge skin of dogs naturally infected by .

Reactivity of sera from dogs living in a leishmaniasis-endemic area to the COOH-terminal region of cysteine proteinase B.

Cysteine proteinases are well-known virulence factors of Leishmania spp. with demonstrated actions in both experimental mouse infection and human infection. However, studies on these enzymes in canine leishmaniasis are scarce.

The combination therapy of meglumine antimoniate and oxiranes (epoxy-α-lapachone and epoxymethyl-lawsone) enhance the leishmanicidal effect in mice infected by Leishmania (Leishmania) amazonensis.

Current treatment of cutaneous leishmaniasis includes pentavalent antimonials as first-line drugs, but this therapy has shown severe adverse effects. An alternative to minimize this issue is based on combination therapy scheme with other drugs. In this study we analyzed the potential of the association of meglumine antimoniate (MA) with the oxiranes epoxy-α-lapachone (LAP) or epoxymethyl-lawsone (LAW).

Serine Proteinases in Leishmania (Viannia) braziliensis Promastigotes Have Distinct Subcellular Distributions and Expression.

Serine proteinases in promastigotes were assessed in this work. This study included the investigation of the enzymatic activity of subcellular fractions obtained from benzamidine affinity chromatography, reverse transcription polymerase chain reactions, and in silico assays of subcellular localization of subtilisin. Promastigote serine proteinases showed gelatinolytic activity with molecular masses of 43 kDa to 170 kDa in the cytosolic fraction and 67 kDa to 170 kDa in the membranous fraction.

Insights into the tracking of the cysteine proteinase B COOH-terminal polypeptide of Leishmania (Leishmania) amazonensis by surface plasmon resonance.

Leishmania (Leishmania) amazonensis has adaptive mechanisms to the host environment that are guided by its proteinases, including cysteine proteinase B (CPB), and primarily its COOH-terminal region (Cyspep). This work aimed to track the fate of Cyspep by surface plasmon resonance (SPR) of promastigotes and amastigotes to gain a greater understanding of the adaptation of this parasite in both hosts. This strategy consisted of antibody immobilization on a COOH1 surface, followed by interaction with parasite proteins and epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64).

Antileishmanial Activity of 2-Methoxy-4H-spiro-[naphthalene-1,2'-oxiran]-4-one (Epoxymethoxy-lawsone): A Promising New Drug Candidate for Leishmaniasis Treatment.

Epoxymethoxylawsone is a naphthoquinone derivative promising as drug candidate for the treatment of leishmaniases. In the present work the effectiveness of epoxymethoxylawsone, and meglumine antimoniate on () parasites and on mice paw lesions of infected BALB/c mice was assessed. In an intracellular amastigotes assay, the half-maximal inhibitory concentration (IC) value for epoxymethoxylawsone was slightly higher (1.

Understanding serine proteases implications on Leishmania spp lifecycle.

Serine proteases have significant functions over a broad range of relevant biological processes to the Leishmania spp lifecycle. Data gathered here present an update on the Leishmania spp serine proteases and the status of these enzymes as part of the parasite degradome. The serine protease genes (n = 26 to 28) in Leishmania spp, which encode proteins with a wide range of molecular masses (35 kDa-115 kDa), are described along with their degrees of chromosomal and allelic synteny.

Evidence for Tissue Toxicity in BALB/c Exposed to a Long-Term Treatment with Oxiranes Compared to Meglumine Antimoniate.

Leishmaniasis remains a serious public health problem in developing countries without effective control, whether by vaccination or chemotherapy. Part of the failure of leishmaniasis control is due to the lack of new less toxic and more effective drugs able to eliminate both the lesions and the parasite. Oxiranes derived from naphthoquinones now being assayed are promising drugs for the treatment of this group of diseases.