RÉSUMÉ
Self-assembly involves a set of molecules spontaneously interacting in a highly coordinated and dynamic manner to form a specific supramolecular structure having new and clearly defined properties. Many examples of this occur in nature and many more came from research laboratories, with their number increasing every day via ongoing research concerning complex biomolecules and the possibility of harnessing it when developing new applications. As a phenomenon, self-assembly has been described on very different types of molecules (biomolecules including), so this review focuses on what is known about peptide self-assembly, its origins, the forces behind it, how the properties of the resulting material can be tuned in relation to experimental considerations, some biotechnological applications (in which the main protagonists are peptide sequences capable of self-assembly) and what is yet to be tuned regarding their research and development.
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Biotechnologie , Peptides , Peptides/composition chimique , Biotechnologie/méthodes , Développement de vaccinRÉSUMÉ
Invasive fungal infections (IFIs) caused by Candida species are an emerging threat globally, given that patients at-risk and antifungal resistance are increasing. Antimicrobial peptides (AMPs) have shown good therapeutic capacity against different multidrug-resistant (MDR) microorganisms. This study evaluated the activity of the synthetic peptide, PNR20, against Candida albicans ATCC 10231 and a MDR Colombian clinical isolate of Candida auris. Perturbation of yeast cell surface was evaluated using scanning electron microscopy. Cell viability of Vero cells was determined to assess peptide toxicity. Additionally, survival, fungal burden, and histopathology of BALB/c mice infected intravenously with each Candida species and treated with PNR20 were analyzed. Morphological alterations were identified in both species, demonstrating the antifungal effect of PNR20. In vitro, Vero cells' viability was not affected by PNR20. All mice infected with either C. albicans or C. auris and treated with PNR20 survived and had a significant reduction in the fungal burden in the kidney compared to the control group. The histopathological analysis in mice infected and treated with PNR20 showed more preserved tissues, without the presence of yeast, compared to the control groups. This work shows that the utilization of PNR20 is a promising therapeutic alternative against disseminated candidiasis.
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NRAMP1 and VDR gene polymorphisms have been variably associated with susceptibility to tuberculosis (TB) amongst populations having different genetic background. NRAMP1 and VDR gene variants' association with susceptibility to active infection by Mycobacterium tuberculosis (Mtb) was analyzed in the Warao Amerindian population, an ethnic population from Venezuela's Orinoco delta region. Genomic DNA was extracted from individuals with and without TB to evaluate genetic polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Four NRAMP1 gene polymorphisms were analyzed: D543N (rs17235409), 3' UTR (rs17235416), INT4 (rs3731865), and 274C/T (rs2276631), and one VDR gene polymorphism: FokI (rs2228570). The results showed that the genotypes D543N-A/A, 3'UTR-TGTG+/+, INT4-C/C, and 274C/T-T/T of known polymorphism in the NRAMP1 gene, as well as the genotypes FokI-F/f and FokI-f/f in the VDR gene were most often found in indigenous Warao with active TB. Binomial logistic regression was used for evaluating associations between polymorphisms and risk of contracting TB, an association between NRAMP1-D543N-A/A genotype distribution and TB susceptibility was found in Warao Amerindians. Regarding Venezuelan populations having different genetic backgrounds; statistically significant TB associations concerning NRAMP1-D543N-A/A, INT4-C/C and 3'UTR-TGTG+/+ variant genotype distributions in Warao Amerindians (indigenous) compared to Creole (admixed non-indigenous population) individuals were found. In conclusion, the results thus indicated that the association between NRAMP1-D543N-A/A genotype and TB in Warao Amerindians could support such allele's role in host susceptibility to Mtb infection.
Sujet(s)
Transporteurs de cations , Tuberculose , Humains , Régions 3' non traduites/génétique , Venezuela , Prédisposition génétique à une maladie , Transporteurs de cations/génétique , Tuberculose/génétique , Génotype , Études cas-témoinsRÉSUMÉ
Plasmodium falciparum-related malaria represents a serious worldwide public health problem due to its high mortality rates. P. falciparum expresses rhoptry neck protein 4 (PfRON4) in merozoite and sporozoite rhoptries, it participates in tight junction-TJ formation via the AMA-1/RON complex and is refractory to complete genetic deletion. Despite this, which PfRON4 key regions interact with host cells remain unknown; such information would be useful for combating falciparum malaria. Thirty-two RON4 conserved region-derived peptides were chemically synthesised for determining and characterising PfRON4 regions having high host cell binding affinity (high activity binding peptides or HABPs). Receptor-ligand interaction/binding assays determined their specific binding capability, the nature of their receptors and their ability to inhibit in vitro parasite invasion. Peptides 42477, 42479, 42480, 42505 and 42513 had greater than 2% erythrocyte binding activity, whilst peptides 42477 and 42480 specifically bound to HepG2 membrane, both of them having micromolar and submicromolar range dissociation constants (Kd). Cell-peptide interaction was sensitive to treating erythrocytes with trypsin and/or chymotrypsin and HepG2 with heparinase I and chondroitinase ABC, suggesting protein-type (erythrocyte) and heparin and/or chondroitin sulphate proteoglycan receptors (HepG2) for PfRON4. Erythrocyte invasion inhibition assays confirmed HABPs' importance during merozoite invasion. PfRON4 800-819 (42477) and 860-879 (42480) regions specifically interacted with host cells, thereby supporting their inclusion in a subunit-based, multi-antigen, multistage anti-malarial vaccine.
Sujet(s)
Paludisme , Plasmodium falciparum , Animaux , Humains , Plasmodium falciparum/génétique , Protéines de protozoaire/génétique , Protéines de protozoaire/métabolisme , Protéines de transport/métabolisme , Peptides , Érythrocytes/parasitologie , Liaison aux protéines , Mérozoïtes/métabolisme , Hépatocytes/métabolisme , Antigènes de protozoaireRÉSUMÉ
Adjuvants represent one of the most significant biotechnological solutions regarding vaccine development, thereby broadening the amount of candidates which can now be used and tested in vaccine formulations targeting various pathogens, as antigens which were previously discarded due to their low or null immunogenicity can now be included. Adjuvant development research has grown side-by-side with an increasing body of knowledge regarding immune systems and their recognition of foreign microorganisms. Alum-derived adjuvants were used in human vaccines for many years, even though complete understanding of their vaccination-related mechanism of action was lacking. The amount of adjuvants approved for human use has increased recently in line with attempts to interact with and stimulate the immune system. This review is aimed at summarising what is known about adjuvants, focusing on those approved for use in humans, their mechanism of action and why they are so necessary for vaccine candidate formulations; it also discusses what the future may hold in this growing research field.
Sujet(s)
Vaccins , Humains , Adjuvants immunologiques/pharmacologie , Adjuvants pharmaceutiques , Biotechnologie , AntigènesRÉSUMÉ
Mycobacterium tuberculosis is one of the most successful pathogens affecting humans, being the main cause of tuberculosis. It accounts for most infectious agent-related deaths worldwide; it has been estimated that a third of the world's population are bacillus carriers. This pathogen's evolutionary adaptation is mainly due to its ability to block a host's immune system by preventing it using an effective immune response in cases of active tuberculosis. Peptide-based synthetic vaccines represent an alternative for counteracting tuberculosis; however, although peptide antigens can be identified, they are not recognised by a host's immune system. An approach using dendritic cells as immunomodulating agents for increasing synthetic peptides' antigenic capacity has thus been advanced. Dendritic cells obtained from IL to 4- and GM-CSF-treated peripheral blood mononuclear cells were pulsed with synthetic Mtb protein peptides which have been reported as participating in mycobacteria-host interactions; their amino acid sequences were modified to improve MHC-II coupling and thus increase their recognition by a host's immune system. pMHC-II/TCR interaction triggered a lymphocyte response which controlled Mtb intracellular growth in infected macrophages. This work has been aimed at contributing to understanding dendritic cells' role in Mycobacterium tuberculosis protein peptide antigen presentation, thereby increasing individuals' immune response as a means of controlling the disease.
Sujet(s)
Mycobacterium tuberculosis , Tuberculose , Humains , Agranulocytes , Peptides/composition chimique , Macrophages , Cellules dendritiquesRÉSUMÉ
Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex's stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes' perfect fit into MHC-II human (HLADRßÌ1*) or Aotus (Aona DR) molecules. The enormous relevance of several amino acids' physico-chemical characteristics is analysed in-depth, as is data regarding a 26.5 ± 2.5Å distance between the farthest atoms fitting into HLA-DRß1* structures' Pockets 1 to 9, the role of polyproline II-like (PPIIL) structures having their O and N backbone atoms orientated for establishing H-bonds with specific HLA-DRß1*-peptide binding region (PBR) residues. The importance of residues having specific charge and orientation towards the TCR for inducing appropriate immune activation, amino acids' role and that of structures interfering with PPIIL formation and other principles are demonstrated which have to be taken into account when designing immune, protection-inducing peptide structures (IMPIPS) against diseases scourging humankind, malaria being one of them.
Sujet(s)
Vaccins contre le paludisme , Animaux , Humains , Peptides , Aotidae/métabolisme , Récepteurs aux antigènes des cellules T , Électronique , Acides aminésRÉSUMÉ
Insect cell lines represent a promising and expanding field as they have several research applications including biotechnology, virology, immunity, toxicology, cell signalling mechanisms and evolution. They constitute a powerful tool having a direct impact on human and veterinary medicine and agriculture. Although more than 1000 cell lines have currently been established from various insect species, Calliphora vicina-derived fly cell lines are lacking. This study was aimed at establishing a new C. vicina embryonic tissue-derived cell line. Adult flies were collected and embryonated eggs were mechanically homogenised and seeded in four types of culture media (L15, Grace's insect medium, Grace's/L15 and DMEM). Cell growth and morphological characteristics were recorded and cytogenetic and molecular patterns were determined. The CV-062020-PPB cell line was established and was shown to have optimal growth in Grace's/L15 medium. CV-062020-PPB cell monolayers that had been sub-cultured over 16 times consisted of firmly adhering cells having different morphologies; a fibroblast-like shape dominated and the karyotype had a 12-chromosome diploid number. RAPD-PCR analysis of the CV-062020-PPB cell line revealed a high similarity index and strong intraspecific relationship with C. vicina adult flies and a weaker relationship with the Lutzomyia longipalpis-derived cell line (Lulo). The CV-062020-PPB cell line constitutes the first cell line obtained from C. vicina embryonic tissues and represents an important basic and applied research tool.
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Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (nâπ* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.
Sujet(s)
COVID-19 , Vaccins contre le paludisme , Séquence d'acides aminés , Vaccins contre la COVID-19 , Antigènes d'histocompatibilité de classe II/génétique , Humains , Imidazoles , Peptides , SARS-CoV-2/génétique , Sulfonamides , ThiophènesRÉSUMÉ
Diagnosis and treatment of active tuberculosis (ATB) as well as latent tuberculosis infection (LTBI) are required for effective tuberculosis (TB) control, especially in TB endemic area. The usefulness of conventional tests to distinguish between ATB and LTBI has remained challenging. The present study was aimed to demonstrate the usefulness of the serological response to synthetic peptides from Mycobacterium tuberculosis (Mtb) antigens for discrimination between ATB and LTBI in Warao Amerindians. Serum IgG antibody levels were measured by the indirect ELISA assay using 22 designed and synthesized peptides derived from immunogenic Mtb ESAT-6 and Ag85A proteins. A total of 211 adult Warao Amerindians were included; cases with active TB (ATB, n = 75), latent TB infection (LTBI, n = 85) and non-infected (NI, n = 51). The approach's diagnostic information was compared using receiver operating characteristic (ROC) curves. For ATB diagnostic performance between ATB and NI; ESAT-6; P-12037 had 100% of sensitivity (AUC = 0.812; 0.733 to 0.891 95% CI); and Ag85A; P-10997 had 100% of specificity (AUC = 0.691; 0.597 to 0.785 95% CI); and ATB and LTBI; Ag85A; P-29878 had 100% of sensitivity (AUC = 0.741; 0.666-0.817 95% CI), and P-29879 had 99% of specificity (AUC = 0.679; 0.593-0.765 95% CI). While that ESAT-6 P-12037 also allowed differentiation between LTBI and NI or healthy ones. It had 98.8% of sensitivity and 98.0% of specificity (AUC = 0.640; 0.545-0.735 95% CI). The potential of combination-antigen immunoassays with peptides could discriminate between Warao Amerindians with ATB, LTBI and NI. Further validation of this approach could lead to developing a complementary tool for rapid diagnosis of TB infections.
RÉSUMÉ
Antimicrobial peptides (AMPs) represent a promising and effective alternative for combating pathogens, having some advantages compared to conventional antibiotics. However, AMPs must also contend with complex and specialised Gram-negative bacteria envelops. The variety of lipopolysaccharide and phospholipid composition in Gram-negative bacteria strains and species are decisive characteristics regarding their susceptibility or resistance to AMPs. Such biological and structural barriers have created delays in tuning AMPs to deal with Gram-negative bacteria. This becomes even more acute because little is known about the interaction AMP-Gram-negative bacteria and/or AMPs' physicochemical characteristics, which could lead to obtaining selective molecules against Gram-negative bacteria. As a consequence, available AMPs usually have highly associated haemolytic and/or cytotoxic activity. Only one AMP has so far been FDA approved and another two are currently in clinical trials against Gram-negative bacteria. Such a pessimistic panorama suggests that efforts should be concentrated on the search for new molecules, designs and strategies for combating infection caused by this type of microorganism. This review has therefore been aimed at describing the currently available AMPs for combating Gram-negative bacteria, exploring the characteristics of these bacteria's cell envelop hampering the development of new AMPs, and offers a perspective regarding the challenges for designing new AMPs against Gram-negative bacteria.
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Congenital long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of the QT interval and T-wave abnormalities, caused, in most cases, by mutations in KCNQ1, KCNH2, and SCN5A. Although the predominant pattern of LQTS inheritance is autosomal dominant, compound heterozygous mutations in genes encoding potassium channels have been reported, often with early disease onset and more severe phenotypes. Since the molecular mechanisms underlying severe phenotypes in carriers of compound heterozygous mutations are unknown, it is possible that these compound mutations lead to synergistic or additive alterations to channel structure and function. In this study, all-atom molecular dynamic simulations of KCNQ1 and hERG channels were carried out, including wild-type and channels with compound mutations found in two patients with severe LQTS phenotypes and limited family history of the disease. Because channels can likely incorporate different subunit combinations from different alleles, there are multiple possible configurations of ion channels in LQTS patients. This analysis allowed us to establish the structural impact of different configurations of mutant channels in the activated/open state. Our data suggest that channels with these mutations show moderate changes in folding energy (in most cases of stabilizing character) and changes in channel mobility and volume, differentiating them from each other and from WT. This would indicate possible alterations in K+ ion flow. Hetero-tetrameric mutant channels showed intermediate structural and volume alterations vis-à-vis homo-tetrameric channels. These findings support the hypothesis that hetero-tetrameric channels in patients with compound heterozygous mutations do not necessarily lead to synergistic structural alterations.
Sujet(s)
Canalopathies/génétique , Canal potassique ERG1/métabolisme , Canal potassique KCNQ1/métabolisme , Syndrome du QT long/génétique , Simulation de dynamique moléculaire , Enfant , Enfant d'âge préscolaire , Canal potassique ERG1/génétique , Humains , Canal potassique KCNQ1/génétique , MâleRÉSUMÉ
Thirty-five peptides selected from functionally-relevant SARS-CoV-2 spike (S), membrane (M), and envelope (E) proteins were suitably modified for immunising MHC class II (MHCII) DNA-genotyped Aotus monkeys and matched with HLA-DRß1* molecules for use in humans. This was aimed at producing the first minimal subunit-based, chemically-synthesised, immunogenic molecules (COLSARSPROT) covering several HLA alleles. They were predicted to cover 48.25% of the world's population for 6 weeks (short-term) and 33.65% for 15 weeks (long-lasting) as they induced very high immunofluorescent antibody (IFA) and ELISA titres against S, M and E parental native peptides, SARS-CoV-2 neutralising antibodies and host cell infection. The same immunological methods that led to identifying new peptides for inclusion in the COLSARSPROT mixture were used for antigenicity studies. Peptides were analysed with serum samples from patients suffering mild or severe SARS-CoV-2 infection, thereby increasing chemically-synthesised peptides' potential coverage for the world populations up to 62.9%. These peptides' 3D structural analysis (by 1H-NMR acquired at 600 to 900 MHz) suggested structural-functional immunological association. This first multi-protein, multi-epitope, minimal subunit-based, chemically-synthesised, highly immunogenic peptide mixture highlights such chemical synthesis methodology's potential for rapidly obtaining very pure, highly reproducible, stable, cheap, easily-modifiable peptides for inducing immune protection against COVID-19, covering a substantial percentage of the human population.
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Vaccins contre la COVID-19/immunologie , COVID-19/immunologie , Protéines d'enveloppe des coronavirus/immunologie , Protéines M des coronavirus/immunologie , Glycoprotéine de spicule des coronavirus/immunologie , Vaccins sous-unitaires/immunologie , Animaux , Anticorps neutralisants/sang , Anticorps neutralisants/immunologie , Anticorps antiviraux/sang , Anticorps antiviraux/immunologie , Aotidae , COVID-19/prévention et contrôle , Chaines HLA-DRB1/génétique , Humains , Peptides/immunologie , SARS-CoV-2/immunologieRÉSUMÉ
Viruses have been implicated in cancer development in both humans and animals. The role of viruses in cancer is typically to initiate cellular transformation through cellular DNA damage, although specific mechanisms remain unknown. Silent and long-term viral infections need to be present, in order to initiate cancer disease. In efforts to establish a causative role of viruses, first is needed to demonstrate the strength and consistency of associations in different populations. The aim of this study was to determine the association of bovine leukemia virus (BLV), a causative agent of leukemia in cattle, with breast cancer and its biomarkers used as prognosis of the severity of the disease (Ki67, HER2, hormonal receptors) in Colombian women. An unmatched, observational case-control study was conducted among women undergoing breast surgery between 2016-2018. Malignant samples (n = 75) were considered as cases and benign samples (n = 83) as controls. Nested-liquid PCR, in-situ PCR and immunohistochemistry were used for viral detection in blood and breast tissues. For the risk assessment, only BLV positive samples from breast tissues were included in the analysis. BLV was higher in cases group (61.3%) compared with controls (48.2%), with a statistically significant association between the virus and breast cancer in the unconditional logistic regression (adjusted-OR = 2.450,95%CI:1.088-5.517, p = 0.031). In this study, BLV was found in both blood and breast tissues of participants and an association between breast cancer and the virus was confirmed in Colombia, as an intermediate risk factor.
Sujet(s)
Tumeurs du sein/anatomopathologie , Virus de la leucémie bovine/isolement et purification , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Aire sous la courbe , Région mammaire/anatomopathologie , Région mammaire/virologie , Tumeurs du sein/diagnostic , Tumeurs du sein/virologie , Études cas-témoins , Colombie , Femelle , Humains , Virus de la leucémie bovine/génétique , Modèles logistiques , Adulte d'âge moyen , Réaction de polymérisation en chaîne , Pronostic , ARN viral/analyse , ARN viral/sang , ARN viral/métabolisme , Courbe ROC , Facteurs de risque , Jeune adulteRÉSUMÉ
BACKGROUND: There has been a long-standing debate over the taxonomic status of Rhipicephalus sanguineus sensu lato. Different studies worldwide have reported the occurrence of different well-defined lineages, in addition to Rhipicephalus sanguineus sensu stricto. To date, there are very few studies examining the diverse aspects of this tick in Colombia. We assessed the population structure and genetic diversity of R. sanguineus s.l. in eight departmental regions across Colombia. METHODS: A total of 170 ticks were collected from dogs in different departments of Colombia. All specimens were morphologically compatible with R. sanguineus s.l. and subjected to genetic analysis. DNA sequences were obtained for the 12S rDNA, cytochrome oxidase I (COI) and internal transcribed spacer 2 (ITS2) markers. A concatenated set of all mitochondrial markers was also constructed. Next, maximum likelihood phylogenetic trees were constructed using the sequences generated herein and sequences available in GenBank. Finally, we assessed different summary statistics and analysed population structure and divergence with Fst and Dxy and demographic changes with Tajima's D and Fu and Li's statistical tests. RESULTS: Analysis of the 12S rDNA and COI revealed that all R. sanguineus s.l. specimens collected across different regions of Colombia clustered within the tropical lineage. Micro-geographical analyses showed that the tick population from Amazonas formed a distinct cluster separated from the other sequences, with moderate Fst and Dxy values. However, no signs of a robust population structure were found within the country. The results of Fu's FS tests, together with the haplotype networks and diversity values, signal a possible population expansion of this tick species in Colombia. CONCLUSIONS: Evidence provided herein supports the tropical lineage as the main circulating lineage in Colombia, exhibiting a general lack of genetic structure except for the Amazonas region.
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Variation génétique , Rhipicephalus sanguineus/classification , Rhipicephalus sanguineus/génétique , Infestations par les tiques/médecine vétérinaire , Animaux , Colombie , ADN intergénique/génétique , Démographie , Chiens/parasitologie , Complexe IV de la chaîne respiratoire/génétique , Phylogenèse , ARN ribosomique 16S/génétique , Analyse de séquence d'ADNRÉSUMÉ
BACKGROUND: The inappropriate use of antibiotics has led to the accelerated growth of resistance to antibiotics. The search for new therapeutic strategies (i.e., antimicrobial peptides-AMPs) has thus become a pressing need. OBJECTIVE: Characterising and evaluating Sarconesiopsis magellanica larval fat body-derived AMPs. METHODS: Fat body extracts were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC); mass spectrometry was used for characterising the primary structure of the AMPs so found. ProtParam (Expasy) was used for analysing the AMPs' physico-chemical properties. Synthetic AMPs' antibacterial activity was evaluated. FINDINGS: Four new AMPs were obtained and called sarconesin III, IV, V and VI. Sarconesin III had an α-helix structure and sarconesins IV, V and VI had linear formations. Oligomer prediction highlighted peptide-peptide interactions, suggesting that sarconesins III, V and VI could form self-aggregations when in contact with the microbial membrane. AMPs synthesised from their native molecules' sequences had potent activity against Gram-positive bacteria and, to a lesser extent, against Gram-negative and drug-resistant bacteria. Sarconesin VI was the most efficient AMP. None of the four synthetic AMPs had a cytotoxic effect. MAIN CONCLUSIONS: S. magellanica larval fat body-derived antimicrobial peptides are an important source of AMPs and could be used in different antimicrobial therapies and overcoming bacterial resistance.
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Diptera , Animaux , Antibactériens/pharmacologie , Calliphoridae , Corps gras , Larve , Tests de sensibilité microbienne , PerforinesRÉSUMÉ
BACKGROUND: Tuberculosis (TB) is being underdetected in children as most are smear-negative. This work was aimed at evaluating ESAT-6 and Ag85A synthetic peptides' serodiagnostic potential for diagnosing children having a clinical suspicion of TB. METHODS: The study involved 438 children: 77 Creole nonindigenous (13 suspected of having TB and 64 healthy ones) and 361 Warao indigenous children (39 suspected of TB and 322 healthy children). The approach's diagnostic information was compared using operational characteristics and receiver-operating characteristic (ROC) curves. RESULTS: Ag85A P-29879 had 94.6% sensitivity (AUC = 0.741: 0.651 to 0.819 95% CI) in indigenous children. ESAT-6 P-12036 and P-12037 had 100% and 92.3% of sensitivity (AUC = 0.929: 0.929: 0.846 to 0.975 95% CI and 0.791: 63.9 to 98.7 95% CI, respectively) in Creole children. ESAT-6 peptides also allowed a differentiation between children with TB and healthy ones. CONCLUSIONS: Further validation of this approach could lead to developing a complementary tool for rapid TB diagnosis in children.
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Acyltransferases/composition chimique , Antigènes bactériens/composition chimique , Protéines bactériennes/composition chimique , Peptides/composition chimique , Tuberculose/diagnostic , Adolescent , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Tuberculose/immunologieRÉSUMÉ
HLA class II (HLA-II) genes' polymorphism influences the immune response to Chlamydia trachomatis (Ct), it is considered a sexually transmitted infection. However, associations between HLA-II alleles and Ct-infection have been little explored in humans; this study was thus aimed at determining HLA-DRB1-DQB1 alleles/haplotypes' effect on Ct-infection outcome in a cohort of Colombian women. Cervical sample DNA was used as template for detecting Ct by PCR and typing HLA-DRB1-DQB1 alleles/haplotypes by Illumina MiSeq sequencing. Survival models were adjusted for identifying the alleles/haplotypes' effect on Ct-outcome; bioinformatics tools were used for predicting secreted bacterial protein T- and B-cell epitopes. Sixteen HLA-DRB1 alleles having a significant effect on Ct-outcome were identified in the 262 women analysed. DRB1*08:02:01G and DRB1*12:01:01G were related to infection-promoting events. Only the DQB1*05:03:01G allele related to clearance/persistence events was found for HLA-DQB1. HLA-DRB1 allele homozygous women were associated with events having a lower probability of clearance and/or early occurrence of persistence. Twenty-seven peptides predicted in silico were associated with protective immunity against Ct; outer membrane and polymorphic membrane protein-derived peptides had regions having dual potential for being T- or B-cell epitopes. This article describes HLA-DRB1-DQB1 alleles/haplotypes related to Ct-infection resolution and the peptides predicted in silico which might probably be involved in host immune response. The data provides base information for developing future studies leading to the development of effective prevention measures against Ct-infection.
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Allèles , Infections à Chlamydia/étiologie , Chlamydia trachomatis , Prédisposition génétique à une maladie , Chaines bêta des antigènes HLA-DQ/génétique , Chaines HLA-DRB1/génétique , Peptides/génétique , Adulte , Séquence d'acides aminés , Cartographie épitopique , Épitopes , Femelle , Fréquence d'allèle , Chaines bêta des antigènes HLA-DQ/composition chimique , Chaines HLA-DRB1/composition chimique , Haplotypes , Humains , Estimation de Kaplan-Meier , Mâle , Adulte d'âge moyen , Peptides/composition chimique , Jeune adulteRÉSUMÉ
Bovine leukemia virus (BLV) is the causative agent of leukemia/lymphoma in cattle. It has been found in humans and cattle-derived food products. In humans, it is described as a potential risk factor for breast cancer development. However, the transmission path remains unclear. Here, a molecular epidemiology analysis was performed to identify signatures of genetic flux of BLV among humans, animals, and food products. Sequences obtained from these sources in Colombia were used (n = 183) and compared with reference sequences available in GenBank. Phylogenetic reconstruction was performed in IQ-TREE software with the maximum likelihood algorithm. Haplotype (hap) distribution among the population was carried out with a median-joining model in Network5.0. Recombination events were inferred using SplitsTree4 software. In the phylogenetic analysis, no specific branches were identified for the Colombian sequences or for the different sources. A total of 31 haps were found, with Hap 1, 4, 5 and 7 being shared among the three sources of the study. Reticulation events among the different sources were also detected during the recombination analysis. These results show new insights about the zoonotic potential of BLV, showing evidence of genetic flux between cattle and humans. Prevention and control strategies should be considered to avoid viral dissemination as part of the One Health program policies.
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Leucose bovine enzootique , Virus de la leucémie bovine , Animaux , Bovins , Colombie/épidémiologie , Leucose bovine enzootique/épidémiologie , Leucose bovine enzootique/génétique , Haplotypes , Humains , Virus de la leucémie bovine/génétique , PhylogenèseRÉSUMÉ
Experimentally estimating peptide-major histocompatibility complex (pMHC) binding affinity has been quite challenging due to the many receptors and the many potential ligands implicated in it. We have thus proposed a straightforward computational methodology considering the different mechanisms involved in pMHC binding to facilitate studying such receptor-ligand interactions. We have developed a pipeline using semi-empirical quantum mechanical methods for calculating pMHC class I and II molecules' binding energy (BE). This pipeline can systematize the methodology for calculating pMHC system BE, enabling the rational design of T-cell epitopes to be used as pharmaceuticals and vaccines.