A Brief View of the Surface Membrane Proteins from<i>Trypanosoma cruzi</i>

Pech-Canul, Ángel de la Cruz; Monteón, Vı́ctor; Solís-Oviedo, Rosa-Lidia

doi:10.1155/2017/3751403

Cited by 42 publications

(50 citation statements)

References 149 publications

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“…Micelles are not real mimetics of membranes. Thus, in order to discard any influence of the high curvature of these structures, the peptides were evaluated in unilamellar vesicles, mimicking both microorganisms/human eukaryotic (POPC-zwuitterionic lipid) or fungal/parasitic (POPC:POPS-negative charge) cell membranes [60,61]. The outer mammalian membranes are composed of lipids that primarily have neutral charges (POPC).…”

Section: Circular Dichroismmentioning

confidence: 99%

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group

et al. 2020

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Parasitic diseases are a neglected and serious problem, especially in underdeveloped countries. Among the major parasitic diseases, Leishmaniasis figures as an urgent challenge due to its high incidence and severity. At the same time, the indiscriminate use of antibiotics by the population is increasing together with resistance to medicines. To address this problem, new antibiotic-like molecules that directly kill or inhibit the growth of microorganisms are necessary, where antimicrobial peptides (AMPs) can be of great help. In this work, the ferrocene molecule, one active compound with low levels of in vivo toxicity, was coupled to the N-terminus of the RP1 peptide (derived from the human chemokine CXCL4), aiming to evaluate how this change modifies the structure, biological activity, and toxicity of the peptide. The peptide and the conjugate were synthesized using the solid phase peptide synthesis (SPPS). Circular dichroism assays in PBS showed that the RP1 peptide and its conjugate had a typical spectrum for disordered structures. The Fc-RP1 presented antiamastigote activity against Leishmania amazonensis (IC 50 = 0.25 μmol L -1 ). In comparison with amphotericin B, a second-line drug approved for leishmaniasis treatment, (IC 50 = 0.63 μmol L -1 ), Fc-RP1 was more active and showed a 2.5-fold higher selectivity index. The RP1 peptide presented a MIC of 4.3 μmol L -1 against S. agalactiae, whilst Fc-RP1 was four times more active (MIC = 0.96 μmol L -1 ), indicating that ferrocene improved the antimicrobial activity against Gram-positive bacteria. The Fc-RP1 peptide also decreased the minimum inhibitory concentration (MIC) in the assays against E. faecalis (MIC = 7.9 μmol L -1 ), E. coli (MIC = 3.9 μmol L -1 ) and S. aureus (MIC = 3.9 μmol L -1 ). The cytotoxicity of the compounds was tested against HaCaT cells, and no significant activity at the highest concentration tested (500 μg. mL -1 ) was observed, showing the high potential of this new compound as a possible new drug. The coupling of ferrocene also increased the vesicle permeabilization of the peptide, showing a direct relation between high peptide concentration and high carboxyfluorescein release, which indicates the action mechanism by pore formation on the vesicles. Several studies have shown that ferrocene destabilizes cell membranes through lipid peroxidation, leading to cell lysis. It is noteworthy that the Fc-RP1 peptide synthesized here PLOS ONE

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Section: Circular Dichroismmentioning

confidence: 99%

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group

et al. 2020

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“…It is possible that it was missed because the combinatorial library used here was not designed for proteome mapping, even though we explored it. Alternatively, it is because TSSA is expressed only by the infective, bloodstream tryptomastigotes [ 66 ]. The samples analyzed here were from asymptomatic donors; these people were likely to be harboring intracellular amastigotes, associated with the chronic infection.…”

Section: Discussionmentioning

confidence: 99%

An ImmunoSignature test distinguishes Trypanosoma cruzi, hepatitis B, hepatitis C and West Nile virus seropositivity among asymptomatic blood donors

Rowe¹,

Melnick²,

Gerwien³

et al. 2017

PLoS Negl Trop Dis

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BackgroundThe complexity of the eukaryotic parasite Trypanosoma (T.) cruzi manifests in its highly dynamic genome, multi-host life cycle, progressive morphologies and immune-evasion mechanisms. Accurate determination of infection or Chagas’ disease activity and prognosis continues to challenge researchers. We hypothesized that a diagnostic platform with higher ligand complexity than previously employed may hold value.MethodologyWe applied the ImmunoSignature Technology (IST) for the detection of T. cruzi-specific antibodies among healthy blood donors. IST is based on capturing the information in an individual’s antibody repertoire by exposing their peripheral blood to a library of >100,000 position-addressable, chemically-diverse peptides.Principal findingsInitially, samples from two Chagas cohorts declared positive or negative by bank testing were studied. With the first cohort, library-peptides displaying differential binding signals between T. cruzi sero-states were used to train an algorithm. A classifier was fixed and tested against the training-independent second cohort to determine assay performance. Next, samples from a mixed cohort of donors declared positive for Chagas, hepatitis B, hepatitis C or West Nile virus were assayed on the same library. Signals were used to train a single algorithm that distinguished all four disease states. As a binary test, the accuracy of predicting T. cruzi seropositivity by IST was similar, perhaps modestly reduced, relative to conventional ELISAs. However, the results indicate that information beyond determination of seropositivity may have been captured. These include the identification of cohort subclasses, the simultaneous detection and discerning of other diseases, and the discovery of putative new antigens.Conclusions & significanceThe central outcome of this study established IST as a reliable approach for specific determination of T. cruzi seropositivity versus disease-free individuals or those with other diseases. Its potential contribution for monitoring and controlling Chagas lies in IST’s delivery of higher resolution immune-state readouts than obtained with currently-used technologies. Despite the complexity of the ligand presentation and large quantitative readouts, performing an IST test is simple, scalable and reproducible.

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“…For example, satellite DNA is a 195 bp repetitive element that can be used as a T. cruzi infection marker in molecular diagnostics [ 17 ]; however, no function has been attributed to this sequence. Conversely, multigenic families mostly encode surface proteins involved in cell invasion as well as immune system evasion by T. cruzi [ 18 ]. The expression levels of these genes vary along the T. cruzi life cycle according to their function, but little is known about how they are regulated.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Interspersed DNA Repetitive Elements in the Trypanosoma cruzi Genome Associated with the 3′UTRs of Surface Multigenic Families

Calderano

Nishiyama-Jr

Marini

et al. 2020

Genes

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Trypanosoma cruzi is the etiological agent of Chagas disease, which affects millions of people in Latin America. No transcriptional control of gene expression has been demonstrated in this organism, and 50% of its genome consists of repetitive elements and members of multigenic families. In this study, we applied a novel bioinformatics approach to predict new repetitive elements in the genome sequence of T. cruzi. A new repetitive sequence measuring 241 nt was identified and found to be interspersed along the genome sequence from strains of different DTUs. This new repeat was mostly on intergenic regions, and upstream and downstream regions of the 241 nt repeat were enriched in surface protein genes. RNAseq analysis revealed that the repeat was part of processed mRNAs and was predominantly found in the 3′ untranslated regions (UTRs) of genes of multigenic families encoding surface proteins. Moreover, we detected a correlation between the presence of the repeat in the 3′UTR of multigenic family genes and the level of differential expression of these genes when comparing epimastigote and trypomastigote transcriptomes. These data suggest that this sequence plays a role in the posttranscriptional regulation of the expression of multigenic families.

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A Brief View of the Surface Membrane Proteins fromTrypanosoma cruzi

Cited by 42 publications

References 149 publications

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group

An ImmunoSignature test distinguishes Trypanosoma cruzi, hepatitis B, hepatitis C and West Nile virus seropositivity among asymptomatic blood donors

Identification of Novel Interspersed DNA Repetitive Elements in the Trypanosoma cruzi Genome Associated with the 3′UTRs of Surface Multigenic Families

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