RESUMEN
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.
Asunto(s)
Enfermedades de Transmisión Sexual , Trichomonas vaginalis , Vacunas , Humanos , Vacunología , Enfermedades de Transmisión Sexual/prevención & controlRESUMEN
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.
Asunto(s)
Bordetella pertussis , Tos Ferina , Niño , Humanos , Adolescente , Bordetella pertussis/genética , Tos Ferina/prevención & control , Tos Ferina/microbiología , Vacuna contra la Tos Ferina/farmacología , GenómicaRESUMEN
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.
Asunto(s)
Rickettsia , Vacunas , Animales , Genoma Bacteriano/genética , Genómica , Humanos , Rickettsia/genética , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. METHODS: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. RESULTS AND CONCLUSION: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.
Asunto(s)
Acetato Quinasa/antagonistas & inhibidores , Antibacterianos/farmacología , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Simulación del Acoplamiento Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Acetato Quinasa/genética , Acetato Quinasa/metabolismo , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Ácidos Carboxílicos/química , Ácidos Carboxílicos/aislamiento & purificación , Ácidos Carboxílicos/farmacología , Ácido Clorogénico/química , Ácido Clorogénico/aislamiento & purificación , Ácido Clorogénico/farmacología , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Furanos/química , Furanos/aislamiento & purificación , Furanos/farmacología , Lignanos/química , Lignanos/aislamiento & purificación , Lignanos/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium tuberculosis/crecimiento & desarrollo , Mycobacterium tuberculosis/metabolismo , Piper betle/química , Piperidinas/química , Piperidinas/aislamiento & purificación , Piperidinas/farmacología , Relación Estructura-ActividadRESUMEN
Prenatal alprazolam (APZ) treatment in 0.1 and 0.2 mg/kg/day doses during 13-20 days of gestation induced significant increase in open-field ambulation, rearings, self-grooming and faecal pellets in rat offspring. Prenatal APZ treated rats displayed significantly increased anxiogenic behaviour on elevated plus maze (spent less time on open arms, more time on enclosed arms and made less number of entries on open arms) and increased anxiogenecity on elevated zero maz e(APZ treated rats spent less time on open arms and made less number of head dips and stretched attend postures in comparison to control rat offspring). The results indicate persistent behavioural alterations in the rat offspring after prenatal exposure to APZ.
Asunto(s)
Alprazolam/toxicidad , Ansiolíticos/toxicidad , Trastornos de Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Animales , Conducta Exploratoria , Femenino , Luz , Intercambio Materno-Fetal , Aprendizaje por Laberinto , Embarazo , RatasRESUMEN
Lipophilic extracts of Ginkgo biloba L. leaves were tested for their possible role on rodent models of depression and stress. Lipophilic extracts of Ginkgo leaves (LEG) at (50 and 100 mg/kg, p.o.) exhibited dose dependent, significant antidepressant activity in the behavioral despair test and learned helplessness rodent model of depression. The activities were comparable to that of imipramine (15 mg/kg) and EGb 761 (50 mg/kg). In the cold immobilization stress induced gastric ulcer model of stress, only the LEG showed a significant reduction in the ulcer index. GC-MS characterization of this bioactive extract was found to be rich in a group of 6-alkyl salicylates (6-AS), along with a fatty alcohol, fatty acids and cardanols. The n-heptadecenyl salicylate represented 60% of the 6-AS. Notable was the absence of dihydroxy alkylphenols which are linked to allergic reactions similar to the urushiols present in poison ivy. In commercial products of Ginkgo, these dihydroxy phenols as well as the favorable 6-AS are removed during enrichment of flavonol glycosides and terpenic lactones. The current findings suggest that intact carboxylic acid groups containing 6-AS are the bioactive components of the lipophilic extract of Ginkgo leaves with antidepressant and antistress activities.