Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
1.
J Biomol Struct Dyn ; : 1-15, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38239063

RESUMO

Equine strangles is a prevalent disease that affects the upper respiratory in horses and is caused by the Gram-positive bacterium Streptococcus equi. In addition to strangles, other clinical conditions are caused by the two S. equi subspecies, equi and zooepidemicus, which present relevant zoonotic potential. Treatment of infections caused by S. equi has become challenging due to the worldwide spreading of infected horses and the unavailability of effective therapeutics and vaccines. Penicillin treatment is often recommended, but multidrug resistance issues arised. We explored the whole genome sequence of 18 S. equi isolates to identify candidate proteins to be targeted by natural drug-like compounds or explored as immunogens. We considered only proteins shared among the sequenced strains of subspecies equi and zooepidemicus, absent in the equine host and predicted to be essential and involved in virulence. Of these, 4 proteins with cytoplasmic subcellular location were selected for molecular docking with a library of 5008 compounds, while 6 proteins were proposed as prominent immunogens against S. equi due to their probabilities of behaving as adhesins. The molecular docking analyses revealed the best ten ligands for each of the 4 drug target candidates, and they were ranked according to their binding affinities and the number of hydrogen bonds for complex stability. Finally, the natural 5-ring compound C25H20F3N5O3 excelled in molecular dynamics simulations for the increased stability in the interaction with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB). This research paves the way to developing new therapeutics to minimize the impacts caused by S. equi infections.Communicated by Ramaswamy H. Sarma.

2.
J Fungi (Basel) ; 10(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38248954

RESUMO

Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against Histoplasma, with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine's efficacy in in vivo models.

3.
An Acad Bras Cienc ; 95(suppl 2): e20230617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055447

RESUMO

Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium's genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis.


Assuntos
Infecções Sexualmente Transmissíveis , Trichomonas vaginalis , Vacinas , Humanos , Vacinologia , Infecções Sexualmente Transmissíveis/prevenção & controle
4.
J Biomol Struct Dyn ; : 1-16, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38112302

RESUMO

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37804433

RESUMO

Bacteria of the Leuconostoc genus are Gram-positive bacteria that are commonly found in raw milk and persist in fermented dairy products and plant food. Studies have already explored the probiotic potential of L. mesenteroides, but not from a probiogenomic perspective, which aims to explore the molecular features responsible for their phenotypes. In the present work, probiogenomic approaches were applied in strains F-21 and F-22 of L. mesenteroides isolated from human milk to assess their biosafety at the molecular level and to correlate molecular features with their potential probiotic characteristics. The complete genome of strain F-22 is 1.99 Mb and presents one plasmid, while the draft genome of strain F-21 is 1.89 Mb and presents four plasmids. A high percentage of average nucleotide identity among other genomes of L. mesenteroides (≥ 96%) corroborated the previous taxonomic classification of these isolates. Genomic regions that influence the probiotic properties were identified and annotated. Both strains exhibited wide genome plasticity, cell adhesion ability, proteolytic activity, proinflammatory and immunomodulation capacity through interaction with TLR-NF-κB and TLR-MAPK pathway components, and no antimicrobial resistance, denoting their potential to be candidate probiotics. Further, the strains showed bacteriocin production potential and the presence of acid, thermal, osmotic, and bile salt resistance genes, indicating their ability to survive under gastrointestinal stress. Taken together, our results suggest that L. mesenteroides F-21 and F-22 are promising candidates for probiotics in the food and pharmaceutical industries.

6.
Mol Divers ; 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658910

RESUMO

Listeria monocytogenes is an important human and animal pathogen able to cause an infection named listeriosis and is mainly transmitted through contaminated food. Among its virulence traits, the ability to form biofilms and to survive in harsh environments stand out and lead to the persistence of L. monocytogenes for long periods in food processing environments. Virulence and biofilm formation are phenotypes regulated by quorum sensing (QS) and, therefore, the control of L. monocytogenes through an anti-QS strategy is promising. This study aimed to identify, by in silico approaches, proteins secreted by lactic acid bacteria (LAB) potentially able to interfere with the agr QS system of L. monocytogenes. The genome mining of Lacticaseibacillus rhamnosus GG and Lactobacillus acidophilus NCFM revealed 151 predicted secreted proteins. Concomitantly, the three-dimensional (3D) structures of AgrB and AgrC proteins of L. monocytogenes were modeled and validated, and their active sites were predicted. Through protein-protein docking and molecular dynamic, Serine-type D-Ala-D-Ala carboxypeptidase and L,D-transpeptidase, potentially secreted by L. rhamnosus GG and L. acidophilus NCFM, respectively, were identified with high affinity to AgrB and AgrC proteins, respectively. By inhibiting the translocation of the cyclic autoinducer peptide (cyclic AIP) via AgrB, and its recognition in the active site of AgrC, these LAB proteins could disrupt L. monocytogenes communication by impairing the agr QS system. The application of the QS inhibitors predicted in this study can emerge as a promising strategy in controlling L. monocytogenes in food processing environment and as an adjunct to antibiotic therapy for the treatment of listeriosis.

7.
Res Microbiol ; 174(7): 104086, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37307910

RESUMO

Salmonella Typhimurium is an important agent of foodborne diseases. In Peru, the emergence of multidrug-resistant isolates of S. Typhimurium from the food chain could be linked to guinea pig farming as a potential reservoir and their uncontrolled antibiotic treatment against salmonellosis. In this study, we performed the sequencing, genomic diversity, and characterization of resistance elements transmitted by isolates from farm and meat guinea pigs. The genomic diversity and antimicrobial resistance of S. Typhimurium isolates were performed using nucleotide similarity, cgMLST, serotyping, phylogenomic analyses, and characterization of resistance plasmids. We found at least four populations of isolates from farm guinea pigs and four populations from meat guinea pigs without finding isolated transmission between both resources. Genotypic resistance to antibiotics was observed in at least 50% of the isolates. Among the farm guinea pig isolates, ten were found to be resistant to nalidixic acid, and two isolates exhibited multidrug resistance to aminoglycosides, tetracycline-fluoroquinolone (carrying strA-strB-tetA-tetB genes and gyrA S83F mutation), or trimethoprim-sulfonamide (carrying AaadA1-drfA15-sul1 genes). Additionally, two isolates from the meat source were resistant to fluoroquinolones (one of which had enrofloxacin resistance). The transmissible resistance plasmids with insertion sequences (IS) such as IncI-gamma-K1-ISE3-IS6, IncI1-I (alpha)-IS21-Tn10, and Col (pHAD28) were commonly found in isolates belonging to the HC100-9757 cluster from both guinea pigs and human hosts. Altogether, our work provides resistance determinants profiles and Salmonella sp. circulating lineages using WGS data that can promote better sanitary control and adequate antimicrobial prescription.

8.
Comput Biol Med ; 159: 106941, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37105111

RESUMO

Rotavirus (RV) and Norovirus (NV) are the main viral etiologic agents of acute gastroenteritis (AG), a serious pediatric condition associated with significant death rates and long-term complications. Anti-RV vaccination has been proved efficient in the reduction of severe AG worldwide, however, the available vaccines are all attenuated and have suboptimal efficiencies in developing countries, where AG leads to substantial disease burden. On the other hand, no NV vaccine has been licensed so far. Therefore, we used immunoinformatics tools to develop a multi-epitope vaccine (ChRNV22) to prevent severe AG by RV and NV. Epitopes were predicted against 17 prevalent genotypes of four structural proteins (NV's VP1, RV's VP4, VP6 and VP7), and then assembled in a chimeric protein, with two small adjuvant sequences (tetanus toxin P2 epitope and a conserved sequence of RV's enterotoxin, NSP4). Simulations of the immune response and interactions with immune receptors indicated the immunogenic properties of ChRNV22, including a Th1-biased response. In silico search for putative host-homologous, allergenic and toxic regions also indicated the vaccine safety. In summary, we developed a multi-epitope vaccine against different NV and RV genotypes that seems promising for the prevention of severe AG, which will be further assessed by in vivo tests.


Assuntos
Norovirus , Rotavirus , Vacinas , Criança , Humanos , Rotavirus/genética , Norovirus/genética , Epitopos
9.
Indian J Med Res ; 157(4): 293-303, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37102510

RESUMO

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.


Assuntos
COVID-19 , Ingredientes de Alimentos , Humanos , Nutrigenômica , Dióxido de Carbono , Lipopolissacarídeos , Pandemias , Síndrome da Liberação de Citocina , Ácido Palmítico , SARS-CoV-2 , Dieta/métodos , Comportamento Alimentar , Zinco , Chá , Ferro , Triglicerídeos
10.
J Fungi (Basel) ; 9(2)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36836308

RESUMO

Histoplasma capsulatum is a thermodymorphic fungus that causes histoplasmosis, a systemic mycosis that presents different clinical manifestations, ranging from self-limiting to acute lung infection, chronic lung infection and disseminated infection. Usually, it affects severely immunocompromised patients although immunocompetent patients can also be infected. Currently, there are no vaccines to prevent histoplasmosis and the available antifungal treatment presents moderate to high toxicity. Additionally, there are few options of antifungal drugs. Thus, the aim of this study was to predict possible protein targets for the construction of potential vaccine candidates and predict potential drug targets against H. capsulatum. Whole genome sequences from four previously published H. capsulatum strains were analyzed and submitted to different bioinformatic approaches such as reverse vaccinology and subtractive genomics. A total of four proteins were characterized as good protein candidates (vaccine antigens) for vaccine development, three of which are membrane-bound and one is secreted. In addition, it was possible to predict four cytoplasmic proteins which were classified as good protein candidates and, through molecular docking performed for each identified target, we found four natural compounds that showed favorable interactions with our target proteins. Our study can help in the development of potential vaccines and new drugs that can change the current scenario of the treatment and prevention of histoplasmosis.

11.
Gene ; 855: 147131, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36539044

RESUMO

Staphylococcus aureus is the main etiological agent of mastitis in small ruminants worldwide. This disease has a difficult cure and possible relapse, leading to significant economic losses in production, milk quality and livestock. This study performed comparative genomic analyses between 73 S. aureus genomes from different hosts (human, bovine, pig and others). This work isolated and sequenced 12 of these genomes from ovine. This study contributes to the knowledge of genomic specialization and the role of specific genes in establishing infection in ovine mastitis-associated S. aureus. The genomes of S. aureus isolated from sheep maintained a higher representation when grouped with clonal complexes 130 and 133. The genomes showed high genetic similarity, the species pan-genome consisting of 4200 genes (central = 2008, accessory = 1559 and unique = 634). Among these, 277 unique genes were related to the genomes isolated from sheep, with 39.6 % as hypothetical proteins, 6.4 % as phages, 6.4 % as toxins, 2.9 % as transporters, and 44.7 % as related to other proteins. Furthermore, at the pathogen level, they showed 80 genes associated with virulence factors and 19 with antibiotic resistance shared in almost all isolates. Although S. aureus isolated from ovine showed susceptibility to antimicrobials in vitro, ten genes were predicted to be associated with antibiotic inactivation and efflux pump, suggesting resistance to gentamicin and penicillin. This work may contribute to identifying genes acquired by horizontal transfer and their role in host adaptation, virulence, bacterial resistance, and characterization of strains affecting ovine.


Assuntos
Mastite Bovina , Infecções Estafilocócicas , Feminino , Animais , Bovinos , Ovinos/genética , Humanos , Suínos , Fatores de Virulência/genética , Staphylococcus aureus/genética , Adaptação ao Hospedeiro , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/microbiologia , Ruminantes/genética , Genômica , Sequências Repetitivas Dispersas , Mastite Bovina/genética , Mastite Bovina/microbiologia
12.
J Am Soc Mass Spectrom ; 33(11): 2055-2062, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36239433

RESUMO

Biochemical, serological, and molecular methods have been developed for the laboratory diagnosis of diseases caused by C. pseudotuberculosis (CP), but the identification of the pathogen and biovars differentiation may be time-consuming, expensive, and confusing compared with other bacteria. This study aimed to evaluate MALDI Biotyper and Overall Genome Relatedness Index (OGRI) analysis to optimize the identification and differentiation of biovars of C. pseudotuberculosis. Out of 230 strains isolated from several hosts and countries, 202 (87.8%) were precisely classified using MALDI Biotyper and the BioNumerics platform. The classification accuracies for the Ovis and Equi biovars were 80 (88.75%) and 82 (92.68%), respectively. When analyzing a sampling of these strains by Average Nucleotide Identity based on BLAST and TETRA analyses using genomic sequence data, it was possible to differentiate 100% of the strains in Equi and Ovis. Our data show that MALDI Biotyper and OGRI analysis help identify C. pseudotuberculosis at the species and biovar levels.


Assuntos
Corynebacterium pseudotuberculosis , Ovinos , Animais , Corynebacterium pseudotuberculosis/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
J Genet Eng Biotechnol ; 20(1): 128, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053342

RESUMO

BACKGROUND: Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Most of the affected population lives in low-income countries and may take up to 10 years to show any clinical signs, which is how physicians diagnose it. However, due to progressive cell damage, early diagnosis is very important. The best way to confirm leprosy is through bacilloscopic, which only confirms the diagnosis and has low accuracy or PCR, that requires specialized operators and is expensive. Since the bacteria are fastidious and do not grow in any culture media, therefore, diagnosing leprosy in the lab is still a challenge. In this concern, a recombinant multi-epitope protein can be a beneficial strategy in the management of the diagnosis, as diverse immunogenic epitopes are precisely selected to detect specific antibodies. Therefore, the purposes of the present study were to select immunogenic epitopes from different relevant proteins, with immunogenic properties, and then to construct a recombinant multi-epitope protein that accuses the presence of the antibodies in the early stages of the disease, making it more than appropriate to be applied as a diagnostic tool. RESULTS: We selected 22 common proteins from both species and, using bioinformatics tools, predicted B and T cell epitopes. After multiple filtering and analyzing, we ended up with 29 epitopes {MHC-I (total 18) and MHC-II (total 11)} from 10 proteins, which were then merged into one construct. Its secondary and tertiary structures were also predicted and refined to comprise the amino acid residues in the best conformation possible. The multi-epitope protein construct was stable, non-host homologous, non-allergic, non-toxic, and elicit humoral and cellular responses. It has conformational B cell epitopes and potential to elicit IFN-γ, IL-4, and IL-10 secretion. CONCLUSIONS: This novel recombinant multi-epitope protein constructed using the common epitopes from M. leprae and M. lepromatosis has a huge immunological potential, is stable, and can be lyophilized to be used in ELISA plates or even in biosensors, which are user-friendly diagnosis tools, facilitating translation into human sample tests.

14.
Environ Microbiol ; 24(10): 4714-4724, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35859337

RESUMO

We investigated whether a set of phylogeographical tracked emergent events of Orthocoronavirinae were related to developed, urban and polluted environments worldwide. We explored coronavirus records in response to climate (rainfall parameters), population density, CO2 emission, Human Developmental Index (HDI) and deforestation. We contrasted environmental characteristics from regions with spillovers or encounters of wild Orthocoronavirinae against adjacent areas having best-preserved conditions. We used all complete sequenced CoVs genomes deposited in NCBI and GISAID databases until January 2021. Except for Deltacoronavirus, concentrated in Hong Kong and in birds, the other three genera were scattered all over the planet, beyond the original distribution of the subfamily, and found in humans, mammals, fishes and birds, wild or domestic. Spillovers and presence in wild animals were only reported in developed/densely populated places. We found significantly more occurrences reported in places with higher HDI, CO2 emission, or population density, along with more rainfall and more accentuated seasonality. Orthocoronavirinae occurred in areas with significantly higher human populations, CO2 emissions and deforestation rates than in adjacent locations. Intermediately disturbed ecosystems seemed more vulnerable for Orthocoronavirinae emergence than forested regions in frontiers of deforestation. Sadly, people experiencing poverty in an intensely consumerist society are the most vulnerable.


Assuntos
Infecções por Coronavirus , Coronavirus , Animais , Dióxido de Carbono , Conservação dos Recursos Naturais , Ecossistema , Humanos , Mamíferos
15.
Vaccines (Basel) ; 10(7)2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35891183

RESUMO

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, has seen a resurgence over the past years. T. pallidum is capable of early dissemination and immune evasion, and the disease continues to be a global healthcare burden. The purpose of this study was to design a multi-epitope immunogen through an immunoinformatics-based approach. Multi-epitope immunogens constitute carefully selected epitopes belonging to conserved and essential bacterial proteins. Several physico-chemical characteristics, such as antigenicity, allergenicity, and stability, were determined. Further, molecular docking and dynamics simulations were performed, ensuring binding affinity and stability between the immunogen and TLR-2. An in silico cloning was performed using the pET-28a(+) vector and codon adaptation for E. coli. Finally, an in silico immune simulation was performed. The in silico predictions obtained in this work indicate that this construct would be capable of inducing the requisite immune response to elicit protection against T. pallidum. Through this methodology we have designed a promising potential vaccine candidate for syphilis, namely Tpme-VAC/LGCM-2022. However, it is necessary to validate these findings in in vitro and in vivo assays.

16.
Comput Biol Med ; 142: 105194, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35007945

RESUMO

Pneumonia is a serious global health problem that accounts for over one million deaths annually. Among the main microorganisms causing pneumonia, Mycoplasma pneumoniae is one of the most common ones for which a vaccine is immediately required. In this context, a multi-epitope vaccine against this pathogen could be the best option that can induce effective immune response avoiding any serious adverse reactions. In this study, using an immunoinformatics approach we have designed a multi-epitope vaccine (mpme-VAC/STV-1) against M. pneumoniae. Our designed mpme-VAC/STV-1 is constructed using CTL (cytotoxic T lymphocyte), HTL (Helper T lymphocyte), and B-cell epitopes. These epitopes are selected from the core proteins of 88 M. pneumoniae genomes that were previously identified through reverse vaccinology approaches. The epitopes were filtered according to their immunogenicity, population coverage, and several other criteria. Sixteen CTL/B- and thirteen HTL/B- epitopes that belong to 5 core proteins were combined together through peptide linkers to develop the mpme-VAC/STV-1. The heat-labile enterotoxin from E. coli was used as an adjuvant. The designed mpme-VAC/STV-1 is predicted to be stable, non-toxic, non-allergenic, non-host homologous, and with required antigenic and immunogenic properties. Docking and molecular dynamic simulation of mpme-VAC/STV-1 shows that it can stimulate TLR2 pathway mediated immunogenic reactions. In silico cloning of mpme-VAC/STV-1 in an expression vector also shows positive results. Finally, the mpme-VAC/STV-1 also shows promising efficacy in immune simulation tests. Therefore, our constructed mpme-VAC/STV-1 could be a safe and effective multi-epitope vaccine for immunization against pneumonia. However, it requires further experimental and clinical validations.


Assuntos
Epitopos de Linfócito T , Mycoplasma pneumoniae , Biologia Computacional/métodos , Epitopos de Linfócito T/química , Escherichia coli , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mycoplasma pneumoniae/genética , Vacinas de Subunidades Antigênicas/química
17.
Biochim Biophys Acta Gen Subj ; 1866(4): 130096, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35077824

RESUMO

BACKGROUND: Allergic diseases figure among the most common immune-mediated diseases worldwide, affecting more than 25% of the world's population. Allergic reactions can be triggered by house dust mite (HDM) allergens, of which the so-called group 21 of allergens is considered as clinically relevant. METHODS: Herein, we used a structural bioinformatics and immunoinformatics approach to design hypoallergenic mutant variants of the Der p 21 allergen of Dermatophagoides pteronyssinus, which were then recombinantly expressed in bacteria and tested for their IgE-reactivities. For this, we scanned the wild-type Der p 21 protein for all possible single amino acid substitutions in key IgE-binding regions that could render destabilization of the major epitope regions. RESULTS: Four main substitutions (D82P, K110G, E77G, and E87S) were selected to build mutant variants of the Der p 21 allergen, which were produced in their recombinant forms; two of these variants showed reduced reactivity with IgE. Molecular dynamic simulations and immune simulations demonstrated the overall effects of these mutations on the structural stability of the Der p 21 allergen and on the profile of immune response induced through immunotherapy. CONCLUSIONS: When produced in their recombinant forms, two of the Der p 21 mutant variants, namely proteins K110G and E87S, showed significantly reduced IgE reactivities against sera from HDM-allergic individuals (n = 20; p < 0.001). GENERAL SIGNIFICANCE: This study successfully translated a rational in silico mutagenesis design into low IgE-binding mutant variants of the allergen rDer p 21. These novel hypoallergens are promising to compose next-generation allergen-immunotherapy formulations in near future.


Assuntos
Hipersensibilidade , Imunoglobulina E , Alérgenos/genética , Animais , Antígenos de Dermatophagoides/química , Antígenos de Dermatophagoides/genética , Proteínas de Artrópodes/genética , Humanos , Hipersensibilidade/genética , Imunoglobulina E/genética , Pyroglyphidae/genética , Pyroglyphidae/metabolismo
18.
J Biomol Struct Dyn ; 40(20): 10106-10121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34192477

RESUMO

The Gram-negative bacillus Serratia marcescens, a member of Enterobacteriaceae family, is an opportunistic nosocomial pathogen commonly found in hospital outbreaks that can cause infections in the urinary tract, bloodstream, central nervous system and pneumonia. Because S. marcescens strains are resistant to several antibiotics, it is critical the need for effective treatments, including new drugs and vaccines. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 59 strains of S. marcescens. We found 759 core non-host homologous proteins, of which 87 are putative surface-exposed proteins, 183 secreted proteins, and 80 membrane proteins. From these proteins, we predicted seven candidates vaccine targets: a sn-glycerol-3-phosphate-binding periplasmic protein UgpB, a vitamin B12 TonB-dependent receptor, a ferrichrome porin FhuA, a divisome-associated lipoprotein YraP, a membrane-bound lytic murein transglycosylase A, a peptidoglycan lytic exotransglycosylase, and a DUF481 domain-containing protein. We also predicted two drug targets: a N(4)-acetylcytidine amidohydrolase, and a DUF1428 family protein. Using the molecular docking approach for each drug target, we identified and selected ZINC04259491 and ZINC04235390 molecules as the most favorable interactions with the target active site residues. Our findings may contribute to the development of vaccines and new drug targets against S. marcescens. Communicated by Ramaswamy H. Sarma.


Assuntos
Serratia marcescens , Vacinas , Serratia marcescens/genética , Vacinologia , Simulação de Acoplamento Molecular , Genômica
19.
J Biomol Struct Dyn ; 40(20): 10136-10152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34155952

RESUMO

Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis, a Gram-negative bacterium described over a century ago. Despite broad vaccine coverage and treatment options, the disease is remerging as a public health problem especially in infants and older children. Recent data indicate re-emergence of the disease is related to bacterial resistance to immune defences and decreased vaccine effectiveness, which obviously suggests the need of new effective vaccines and drugs. In an attempt to contribute with solutions to this great challenge, bioinformatics tools were used to genetically comprehend the species of these bacteria and predict new vaccines and drug targets. In fact, approaches were used to analysis genomic plasticity, gene synteny and species similarities between the 20 genomes of Bordetella pertussis already available. Furthermore, it was conducted reverse vaccinology and docking analysis to identify proteins with potential to become vaccine and drug targets, respectively. The analyses showed the 20 genomes belongs to a homogeneous group that has preserved most of the genes over time. Besides that, were found genomics islands and good proteins to be candidates for vaccine and drugs. Taken together, these results suggests new possibilities that may be useful to develop new vaccines and drugs that will help the prevention and treatment strategies of pertussis disease caused by these Bordetella strains. Communicated by Ramaswamy H. Sarma.


Assuntos
Bordetella pertussis , Coqueluche , Criança , Humanos , Adolescente , Bordetella pertussis/genética , Coqueluche/prevenção & controle , Coqueluche/microbiologia , Vacina contra Coqueluche/farmacologia , Genômica
20.
J Biomol Struct Dyn ; 40(16): 7496-7510, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33719856

RESUMO

The genus Rickettsia belongs to the Proteobacteria phylum and these bacteria infect animals and humans causing a range of diseases worldwide. The genus is divided into 4 groups and despite the public health threat and the knowledge accumulated so far, the mandatory intracellular bacteria behaviour and limitation for in vitro culture makes it difficult to create new vaccines and drug targets to these bacteria. In an attempt to overcome these limitations, pan-genomic approaches has used 47 genomes of the genus Rickettsia, in order to describe species similarities and genomics islands. Moreover, we conducted reverse vaccinology and docking analysis aiming the identification of proteins that have great potential to become vaccine and drug targets. We found out that the bacteria of the four Rickettsia groups have a high similarity with each other, with about 90 to 100% of identity. A pathogenicity island and a resistance island were predicted. In addition, 8 proteins were also predicted as strong candidates for vaccine and 9 as candidates for drug targets. The prediction of the proteins leads us to believe in a possibility of prospecting potential drugs or creating a polyvalent vaccine, which could reach most strains of this large group of bacteria.Communicated by Ramaswamy H. Sarma.


Assuntos
Rickettsia , Vacinas , Animais , Genoma Bacteriano/genética , Genômica , Humanos , Rickettsia/genética , Fatores de Virulência/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA