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1.
Methods Mol Biol ; 2265: 591-620, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33704742

RESUMEN

Melanoma accounts for 4% of all skin cancer malignancies, with only 14% of diagnosed patients surviving for more than 5 years after diagnosis. Until now, there is no clear understanding of the detailed molecular contributors of melanoma pathogenesis. Accordingly, more research is needed to understand melanoma development and prognosis.All the treatment approaches that are currently applied have several significant limitations that prevent effective use in melanoma. One major limitation in the treatment of cancer is the acquisition of multidrug resistance (MDR). The MDR results in significant treatment failure and poor clinical outcomes in several cancers, including skin cancer. Treatment of melanoma is especially retarded by MDR. Despite the current advances in targeted and immune-mediated therapy, treatment arms of melanoma are severely limited and stand as a significant clinical challenge. Further, the poor pharmacokinetic profile of currently used chemotherapeutic agents is another reason for treatment failure. Therefore, more research is needed to develop novel drugs and carrier tools for more effective and targeted treatment.Nucleic acid therapy is based on nucleic acids or chemical compounds that are closely related, such as antisense oligonucleotides, aptamers, and small-interfering RNAs that are usually used in situations when a specific gene implicated in a disorder is deemed a therapeutically beneficial target for inhibition. However, the proper application for nucleic acid therapies is hampered by the development of an effective delivery system that can maintain their stability in the systemic circulation and enhance their uptake by the target cells. In this chapter, the prognosis of the different types of melanoma along with the currently used medications is highlighted, and the different types of nucleic acids along with the currently available nanoparticle systems for delivering these nucleic acids into melanoma cells are discussed. We also discuss recently conducted research on the use of different types of nanoparticles for nucleic acid delivery into melanoma cells and highlight the most significant outcomes.


Asunto(s)
Antineoplásicos , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Melanoma/tratamiento farmacológico , Nanopartículas , Ácidos Nucleicos , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Nanopartículas/química , Nanopartículas/uso terapéutico , Ácidos Nucleicos/química , Ácidos Nucleicos/farmacología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología
2.
Expert Opin Drug Metab Toxicol ; 17(3): 291-306, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33544643

RESUMEN

INTRODUCTION: Multi-drug resistance (MDR) is a hindrance toward the successful treatment of cancers. The primary mechanism that gives rise to acquired chemoresistance is the overexpression of adenosine triphosphate-binding cassette (ABC) transporters. The dysregulation of non-coding RNAs (ncRNAs) is a widely concerned reason contributing to this phenotype. AREAS COVERED: In this review, we describe the role of intracellular and exosomal ncRNAs including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in ABC transporters-induced tumor MDR. Meanwhile, we will introduce the potential therapeutic strategies which reverse MDR in terms of reducing the expression of ABC transporters via targeting ncRNAs, like nucleic acid delivery with nanoparticles as well as miRNAs-targeted small molecular compounds. EXPERT OPINION: The dysregulated ncRNAs-mediated overexpression of ABC transporters in chemo-resistant cancer is not negligible. Finding out the underlying mechanism may provide a theoretical basis for clinical therapy of cancer MDR, and the emergence of new approaches for gene therapy targeting ncRNAs to suppress ABC transporters makes reversing cancer MDR possible despite its clinical application requires further investigations. Also, the discovered ncRNAs regulating ABC transporters in chemo-resistant cancers are just a tip of the iceberg of the genetic transcripts, especially for circRNAs, which justify more concern.Abbreviations: MDR, multi-drug resistance; ABC, adenosine triphosphate-binding cassette; NcRNAs, non-coding RNAs; MiRNAs, microRNAs; LncRNAs, long non-coding RNAs; CircRNAs, circular RNAs; CeRNAs, competing endogenous RNAs; 3'UTR, 3'-untranslated regions; SLC, solute carrier; ABCB1/MDR1, ABC subfamily B member 1; ABCG2/BCRP, ABC subfamily G member 2; ABCCs/MRPs, ABC subfamily C 1 to 12; DLL1: Delta-like protein 1; DTX, docetaxel; DOX/ADM/ADR, doxorubicin/adriamycin; PTX, paclitaxel; VBL, vinblastine; VCR, vincristine; MTX, methotrexate; CDDP/DDP, cisplatin/cis-diaminedichloroplatinum; OXA/L-OHP, oxaliplatin; TMZ, temozolomide; 5-FU, 5-fluorouracil; MTA, pemetrexed; NSCLC, non-small cell lung carcinoma; HCC, hepatocellular carcinoma; CRC, colorectal carcinoma; RB, retinoblastoma; RCC, renal cell carcinoma; OS, osteosarcoma; PDAC, pancreatic ductal adenocarcinoma; TNBC, triple-negative breast cancer.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Transportadoras de Casetes de Unión a ATP/genética , Animales , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Humanos , Neoplasias/genética , ARN no Traducido/genética
3.
Cancer Sci ; 112(3): 1196-1208, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33423358

RESUMEN

5-Fluorouracil (5-FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5-FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS-mutant organoids and cell lines in comparison with KRAS wild-type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3-positive patients was significantly worse compared with that of KHDRBS3-negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3-positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage-independent growth by maintaining stem cell-like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/terapia , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Proteínas de Unión al ARN/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Colectomía , Colon/patología , Colon/cirugía , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Receptores de Hialuranos/genética , Masculino , Ratones , Persona de Mediana Edad , Mutación , Células Madre Neoplásicas/patología , Organoides/efectos de los fármacos , Organoides/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas de Unión al ARN/genética , Análisis de Supervivencia , Vía de Señalización Wnt/genética , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Poult Sci ; 100(3): 100887, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33516478

RESUMEN

The extensive use of antibiotics has, in recent years, caused antimicrobial resistance and multidrug resistance in Escherichia coli to gradually develop into a worldwide problem. These resistant E. coli could be transmitted to humans through animal products and animal feces in the environment, thereby creating a problem for bacterial treatment for humans and animals and resulting in a public health issue. Monitoring the resistance of E. coli throughout the broiler fattening period is therefore of great significance for both the poultry industry and public health. In this longitudinal study, samples were taken from 6 conventional broiler fattening farms in Shandong Province, China, at 3 different times within 1 fattening period. The overall isolation rate of E. coli was 53.04% (375/707). Antibiotic resistance was very common in the E. coli isolated from these farms, and differed for different antibiotics, with ampicillin having the highest rate (92.86%) and cefoxitin the lowest (10.12%). Multidrug resistance was as high as 91.07%. More importantly, both the resistance rate of E. coli to the different drugs and the detection rate of drug resistance genes increased over time. The mobile colistin resistance (mcr-1) gene was detected in 24.40% of the strains, and these strains often carried other drug resistance genes, such as those conferring aminoglycoside, ß-lactamase, tetracycline, and sulfonamide resistance. Antimicrobial resistance and drug resistance genes in E. coli were least common in the early fattening stage. The individual detection rates of sul1, sul3, aacC4, aphA3, and mcr-1 were significantly lower (P < 0.05) for the early fattening stage than for the middle and late stages. The rational use of antibiotics, in conjunction with the improvement of the breeding environment during the entire broiler fattening cycle, will be helpful in the development of the poultry industry and the protection of public health.


Asunto(s)
Resistencia a Múltiples Medicamentos , Infecciones por Escherichia coli , Escherichia coli , Enfermedades de las Aves de Corral , Animales , Antibacterianos/farmacología , Pollos , China/epidemiología , Resistencia a Múltiples Medicamentos/genética , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Proteínas de Escherichia coli/genética , Granjas/estadística & datos numéricos , Estudios Longitudinales , Pruebas de Sensibilidad Microbiana/veterinaria , Enfermedades de las Aves de Corral/epidemiología , Enfermedades de las Aves de Corral/microbiología
5.
Anticancer Res ; 40(9): 4921-4928, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32878780

RESUMEN

BACKGROUND/AIM: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. MATERIALS AND METHODS: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. RESULTS: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 µM). Thioridazine was the most potent among the three phenothiazines. CONCLUSION: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Fenotiazinas/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Sinergismo Farmacológico , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/patología , Ratones , Estructura Molecular , Compuestos de Organoselenio/síntesis química , Compuestos de Organoselenio/química , Fenotiazinas/síntesis química , Fenotiazinas/química
6.
PLoS One ; 15(9): e0238390, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32886694

RESUMEN

Pseudomonas aeruginosa has been implicated in a wide range of post-operation wound and lung infections. A wide range of acquired resistance and virulence markers indicate surviving strategy of P. aeruginosa. Complete-genome analysis has been identified as efficient approach towards understanding the pathogenicity of this organism. This study was designed to sequence the entire genome of P. aeruginosa UY1PSABAL and UY1PSABAL2; determine drug-resistance profiles and virulence factors of the isolates; assess factors that contribute toward stability of the genomes; and thereafter determine evolutionary relationships between the strains and other isolates from similar sources. The genomes of the MDR P. aeruginosa UY1PSABAL and UY1PSABAL2 were sequenced on the Illumina Miseq platform. The raw sequenced reads were assessed for quality using FastQC v.0.11.5 and filtered for low quality reads and adapter regions using Trimmomatic v.0.36. The de novo genome assembly was made with SPAdes v.3.13 and annotated using Prokka v.2.1.1 annotation pipeline; Rapid Annotation using Subsytems Technology (RAST) server v.2.0; and PATRIC annotation tool v.3.6.2. Antimicrobial resistance genes and virulence determinants were searched through the functional annotation data generated from Prokka, RAST and PATRIC annotation pipelines; In addition to ResFinder and Comprehensive Antibiotic Resistance Database (CARD) which were employed to determine resistance genes. The PHAge Search Tool Enhanced Release (PHASTER) web server was used for the rapid identification and annotation of prophage sequences within bacterial genome. Predictive secondary metabolites were identified with AntiSMASH v.5.0. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and cas genes regions were also investigated with the CRISPRone and CRISPRFinder server. The genome sizes of 7.0 and 6.4 Mb were determined for UY1PSABAL and UY1PSABAL2 strains with G+C contents of 66.1% and 66.48% respectively. ß-lactamines resistance genes blaPAO, aminoglycoside phosphorylating enzymes genes aph(3')-IIb, fosfomycine resistance gene fosA, vancomycin vanW and tetracycline tetA were among identified resistance genes harboured in both isolates. UY1PSABAL bore additional aph(6)-Id, aph(3'')-Ib, ciprofloxacin-modifying enzyme crpP and ribosomal methylation enzyme rmtB. Both isolates were found harbouring virulence markers such as flagella and type IV pili; and also present various type III secretion systems such as exoA, exoS, exoU, exoT. Secondary metabolites such as pyochelin and pyoverdine with iron uptake activity were found within the genomes as well as quorum-sensing systems, and various fragments for prophages and insertion sequences. Only the UY1PSABAL2 contains CRISPR-Cas system. The phylogeny revealed a very close evolutionary relationship between UY1PSABAL and the similar strain isolated from Malaysia; the same trend was observed between UY1PSABAL2 and the strain from Chinese origin. Complete analyses of the entire genomes provide a wide range of information towards understanding pathogenicity of the pathogens in question.


Asunto(s)
Resistencia a Múltiples Medicamentos/genética , Pseudomonas aeruginosa/genética , Composición de Base , Camerún , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Genoma Bacteriano/genética , Humanos , Filogenia , Profagos/genética , Pseudomonas aeruginosa/aislamiento & purificación , Análisis de Secuencia de ADN , Virulencia/genética , Secuenciación Completa del Genoma/métodos
7.
Ecotoxicol Environ Saf ; 202: 110940, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32800223

RESUMEN

Recent evidence indicates that chronic, low-dose exposure to mixtures of pesticides can cause adverse responses in a variety of cells, tissues and organs, although interactions between pesticides circulating in the blood and cancer cells remain largely unexplored. The aim of this study was to investigate the potential of a mixture of four pesticides to induce multidrug resistance against the chemotherapeutic agents cisplatin, 5-fluorouracil and temozolomide in the human U87 glioblastoma cell line, and to explore the molecular mechanisms underlying this resistance. We found that the repeated administration of the pesticide mixture (containing the insecticides chlorpyrifos-ethyl and deltamethrin, the fungicide metiram, and the herbicide glyphosate) induced a strong drug resistance in U87 cells. The resistance was durable and transferred to subsequent cell generations. In addition, we detected a significant over-expression of the ATP-binding cassette (ABC) membrane transporters P-gp/ABCB1 and BRCP/ABCG2 as well as a glutathione-S-transferase (GST)/M1-type cellular detoxification function, known to have important roles in multidrug resistance, thus providing molecular support for the acquired multidrug resistance phenotype and shedding light on the mechanism of resistance. We further determined that there was lower mortality in the resistant brain tumor cells and that the mitochondrial apoptosis pathway was activated at a lower rate after chemotherapy compared to non-resistant control cells. In addition, multidrug-resistant cells were found to have both higher motility and wound-healing properties, suggesting a greater metastatic potential. Our results suggest that the investigation of P-gp, BRCP and GST/M1 multidrug resistance gene expression and/or protein levels in biopsy specimens of brain tumor patients who were at risk of pesticide exposure could be beneficial in determining chemotherapy dose and prolonging patient survival.


Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Plaguicidas/toxicidad , Pruebas de Toxicidad Crónica , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Glioblastoma/genética , Glioblastoma/patología , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacología
8.
BMC Infect Dis ; 20(1): 533, 2020 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-32698879

RESUMEN

BACKGROUND: Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection. METHODS: A total of 771 blood donors were selected from five districts in the Greater Accra Region, Ghana. Each donor sample was screened with malaria rapid diagnostic test (RDT) kit and parasitaemia quantified microscopically. Dried blood spots from malaria positive samples were genotyped for P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum multi-drug resistance (Pfmdr1), P. falciparum dihydropteroate-synthetase (Pfdhps), P. falciparum dihydrofolate-reductase (Pfdhfr) and Kelch 13 propeller domain on chromosome 13 (Kelch 13) genes. RESULTS: Of the 771 blood donors, 91 (11.8%) were positive by RDT. Analysis of sequence reads indicated successful genotyping of Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes in 84.6, 81.3, 86.8, 86.9 and 92.3% of the isolates respectively. Overall, 21 different mutant haplotypes were identified in 69 isolates (75.8%). In Pfcrt, CVIET haplotype was observed in 11.6% samples while in Pfmdr1, triple mutation (resulting in YFN haplotype) was detected in 8.1% of isolates. In Pfdhfr gene, triple mutation resulting in IRNI haplotype and in Pfdhps gene, quintuple mutation resulting in AGESS haplotype was identified in 17.7% parasite isolates. Finally, five non-synonymous Kelch 13 alleles were detected; C580Y (3.6%), P615L (4.8%), A578S (4.8%), I543V (2.4%) and A676S (1.2%) were detected. CONCLUSION: Results obtained in this study indicated various frequencies of mutant alleles in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes from P. falciparum infected blood donors. These alleles could reduce the efficacy of standard malaria treatment in transfusion-transmitted malaria cases. Incorporating malaria screening into donor screening protocol to defer infected donors is therefore recommended.


Asunto(s)
Donantes de Sangre , Farmacorresistencia Microbiana/genética , Resistencia a Múltiples Medicamentos/genética , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Plasmodium falciparum/genética , Adolescente , Adulto , Alelos , Antimaláricos/uso terapéutico , Enfermedades Asintomáticas , Biomarcadores , Cloroquina/uso terapéutico , Estudios Transversales , Dihidropteroato Sintasa/genética , Femenino , Frecuencia de los Genes , Ghana/epidemiología , Haplotipos , Humanos , Secuencia Kelch/genética , Malaria Falciparum/diagnóstico , Malaria Falciparum/parasitología , Masculino , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Mutación , Plasmodium falciparum/aislamiento & purificación , Prevalencia , Proteínas Protozoarias/genética , Tetrahidrofolato Deshidrogenasa/genética , Adulto Joven
9.
Sci Rep ; 10(1): 6587, 2020 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-32313056

RESUMEN

P-glycoprotein (Pgp), a member of the ATP-binding cassette family, is one of the major causes of multidrug resistance in tumors. Current clinical treatments to overcome MDR involve the co-delivery of a Pgp inhibitor and a chemotherapeutic. A concern for this treatment that has led to varied clinical trial success is the associated systemic toxicities involving endogenous Pgp. Local drug delivery systems, such as in situ forming implants (ISFIs), alleviate this problem by delivering a high concentration of the drug directly to the target site without the associated systemic toxicities. ISFIs are polymeric drug solutions that undergo a phase transition upon injection into an aqueous environment to form a solid drug eluting depot allowing for a high initial intratumoral drug concentration. In this study, we have developed an ISFI capable of overcoming the Pgp resistance by co-delivering a chemotherapeutic, Doxorubicin (Dox), with a Pgp inhibitor, either Pluronic P85 or Valspodar (Val). Studies investigated in vitro cytotoxicity of Dox when combined with either Pgp inhibitor, effect of the inhibitors on release of Dox from implants in PBS, in vivo Dox distribution and retention in a subcutaneous flank colorectal murine tumor, and therapeutic response characterized by tumor growth curves and histopathology. Dox + Val showed a 4-fold reduction in the 50% lethal dose (LD50) after 48 hours. Concurrent delivery of Dox and Val showed the greatest difference at 16 days post injection for both Dox penetration and retention. This treatment group had a 5-fold maximum Dox penetration compared to Dox alone ISFIs (0.53 ± 0.22 cm vs 0.11 ± 0.11 cm, respectively, from the center of the ISFI). Additionally, there was a 3-fold increase in normalized total intratumoral Dox intensity with the Dox + Val ISFIs compared to Dox alone ISFIs (0.54 ± 0.11 vs 0.18 ± 0.09, respectively). Dox + Val ISFIs showed a 2-fold reduction in tumor growth and a 27.69% increase in necrosis 20 days post-injection compared to Dox alone ISFIs. These findings demonstrate that co-delivery of Dox and Val via ISFI can avoid systemic toxicity issues seen with clinical Pgp inhibitors.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Neoplasias Colorrectales/tratamiento farmacológico , Ciclosporinas/farmacología , Poloxaleno/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Humanos , Ratones , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
10.
BMC Infect Dis ; 20(1): 307, 2020 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-32334523

RESUMEN

BACKGROUND: Plasmodium vivax is the most widely distributed malaria parasite, and its drug resistance poses unique challenges to malaria elimination. The Greater Mekong Subregion (GMS) is known as the global epicenter of multidrug resistance. Surveillance of molecular markers associated with drug resistance in this area will help to inform drug policy. METHODS: Dry blood spots from 58 patients out of 109 with P. vivax infection between 2017, December and 2019, March were obtained from Yingjiang County, Yunnan Province, along the China-Myanmar border. Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o were amplified and sequenced to assess gene mutations. The polymorphism and prevalence of these molecular markers were analyzed. RESULTS: Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 27.59, 48.28, 27.59, 32.76 and 48.28% of the isolates, respectively. Single mutant haplotype (I13F57S58T61S99S117I173) was the most frequent (29.31%, 17/58), followed by double mutant haplotype (20.69%, 12/58). Of three types of tandem repeat variations of Pvdhfr, deletion type was the most common. Pvdhps showed a lower prevalence among mutation genotypes. Single mutant was dominant and accounted for 34.48% (20/58). Prevalence of Pvmdr1 mutations at codons 958 and 1076 were 100.00% and 84.48%, respectively. The proportion of double and single mutant types was 84.48% (49/58) and 15.52% (9/58), respectively. Eleven samples (18.97%, 11/58) showed K10 "AAG" insertion in chloroquine resistance transporter gene Pvcrt-o. CONCLUSIONS: There was moderate diversity of molecular patterns of resistance markers of Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o in imported P. vivax cases to Yingjiang county in Western Yunnan, along the China-Myanmar border. Prevalence and molecular pattern of candidate drug resistance markers Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o were demonstrated in this current study, which would help to update drug policy.


Asunto(s)
Malaria Vivax/parasitología , Mutación , Plasmodium vivax/efectos de los fármacos , Plasmodium vivax/genética , Adolescente , Adulto , Anciano , Antimaláricos/uso terapéutico , Biomarcadores , Niño , Preescolar , China , Cloroquina/uso terapéutico , Farmacorresistencia Microbiana/genética , Resistencia a Múltiples Medicamentos/genética , Femenino , Haplotipos , Humanos , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/epidemiología , Masculino , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Plasmodium vivax/aislamiento & purificación , Polimorfismo Genético , Prevalencia , Proteínas Protozoarias/genética , Adulto Joven
11.
Biochem Pharmacol ; 175: 113865, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32142727

RESUMEN

Expression of the ABCG2 multidrug transporter is a marker of cancer stem cells and a predictor of recurrent malignant disease. Understanding how human ABCG2 expression is modulated by pharmacotherapy is crucial in guiding therapeutic recommendations and may aid rational drug development. Genome edited reporter cells are useful in investigating gene regulation and visualizing protein activity in live cells but require precise targeting to preserve native regulatory regions. Here, we describe a fluorescent reporter assay that allows the noninvasive assessment of ABCG2 regulation in human lung adenocarcinoma cells. Using CRISPR-Cas9 gene editing coupled with homology-directed repair, we targeted an EGFP coding sequence to the translational start site of ABCG2, generating ABCG2 knock-out and in situ tagged ABCG2 reporter cells. Using the engineered cell lines, we show that ABCG2 is upregulated by a number of anti-cancer medications, HDAC inhibitors, hypoxia-mimicking agents and glucocorticoids, supporting a model in which ABCG2 is under the control of a general stress response. To our knowledge, this is the first description of a fluorescent reporter assay system designed to follow the endogenous regulation of a human ABC transporter in live cells. The information gained may guide therapy recommendations and aid rational drug design.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Proteína 9 Asociada a CRISPR/genética , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Proteínas de Neoplasias/genética , Células A549 , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Técnicas de Sustitución del Gen , Técnicas de Silenciamiento del Gen , Genes Reporteros , Humanos , Plásmidos
12.
Parasit Vectors ; 13(1): 134, 2020 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-32171326

RESUMEN

BACKGROUND: Insecticide resistance is a growing concern for malaria control and vector control effectiveness relies on assessing it distribution and understanding its evolution. METHODS: We assessed resistance levels and the frequencies of two major target-site mutations, L1014F-VGSC and G119S-ace-1, conferring resistance to pyrethroids (PYRs) and carbamates/organophosphates (CXs/OPs) insecticides. These data were compared to those acquired between 2006 and 2010 to follow resistance evolutionary trends over ten years. RESULTS: We report the results of a 3-year survey (2013-2015) of insecticide resistance in 13 localities across the whole country of Benin. Permethrin (PYR) resistance was found in all populations tested, L1014F-VGSC being almost fixed everywhere, while bendiocarb resistance was limited to a few localities, G119S-ace-1 remaining rare, with very limited variations during surveyed period. Interestingly, we found no effect of the type of insecticide pressure on the dynamics of these mutations. CONCLUSIONS: These results confirm both the high prevalence of PYR resistance and the potential of CXs/OPs as short- to medium-term alternatives in Benin. They also underline the need for regular resistance monitoring and informed management in their usage, as the G119S-ace-1 mutation is already present in Benin and surrounding countries. Their unwise usage would rapidly lead to its spread, which would jeopardize PYR-resistant Anopheles control.


Asunto(s)
Alelos , Anopheles/efectos de los fármacos , Anopheles/genética , Resistencia a Múltiples Medicamentos/genética , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Animales , Benin , Carbamatos/farmacología , Evolución Molecular , Femenino , Proteínas de Insectos/genética , Malaria , Control de Mosquitos/métodos , Mosquitos Vectores/efectos de los fármacos , Mosquitos Vectores/genética , Mutación , Organofosfatos/farmacología , Permetrina/farmacología , Fenilcarbamatos , Piretrinas/farmacología
13.
Sci Rep ; 10(1): 2651, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-32060395

RESUMEN

While direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically progressed, patients still suffer from treatment failures. For the radical eradication of HCV, a deeper understanding of multiple resistance-associated substitutions (RASs) at the single-clone level is essential. To understand HCV quasispecies and their dynamics during DAA treatment, we applied single-molecule real-time (SMRT) deep sequencing on sera from 12 patients with genotype-1b HCV infections with DAA treatment failures, both pre- and post-treatment. We identified >3.2 kbp sequences between NS3 and NS5A genes of 187,539 clones in total, classifying into haplotype codes based on the linkage of seven RAS loci. The number of haplotype codes during the treatment, per sample, significantly decreased from 14.67 ± 9.12 to 6.58 ± 7.1, while the number of nonsynonymous codons on the seven RAS loci, per clone, significantly increased from 1.50 ± 0.92 to 3.64 ± 0.75. In five cases, the minority multi-drug resistant haplotypes at pre-treatment were identical to the major haplotypes at relapse. Moreover, various structural variations (SVs) were detected and their dynamics analysed. These results suggest that SMRT deep sequencing is useful for detecting minority haplotypes and SVs, and to evaluate the dynamics of viral genomes at the single-clone level.


Asunto(s)
Resistencia a Múltiples Medicamentos/genética , Farmacorresistencia Viral/genética , Genoma Viral , Haplotipos/genética , Hepacivirus/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Imagen Individual de Molécula , Antivirales/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Farmacorresistencia Viral/efectos de los fármacos , Humanos
14.
Sci Rep ; 10(1): 1970, 2020 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-32029822

RESUMEN

Chemotherapy, a major cancer treatment approach, suffers seriously from multidrug resistance (MDR), generally caused by innate DNA repair proteins that reverse the DNA modification by anti-cancer therapeutics or trans-membrane efflux proteins that pump anti-cancer therapeutics out of the cytosol. This project focused on finding microRNAs that can regulate MDR proteins by managing corresponding mRNA levels through post-transcriptional regulation based on nucleotide sequence matching. Screening was done with bioinformatics databases for unpublished/unexplored microRNAs with high nucleotide sequence correspondence to two representative MDR proteins, MGMT (a DNA repair protein) and ABCB1 (an efflux protein), revealing microRNA-4539 and microRNA-4261 respectively. To investigate the enhancement of chemotherapeutics in cancer cells, high MGMT expressing glioblastoma (T98G) and a high ABCB1 expressing triple-negative breast cancer cell line (MDA-MB-231-luc) were treated with varying concentrations of chemotherapeutics and corresponding miRNAs. Newly identified MDR-related miRNAs (MDRmiRs) enhanced the response to anti-cancer therapeutics and resulted in effective cell death. In this study, we demonstrated that therapeutic miRNAs could be identified based on the nucleotide sequence matching of miRNAs to targeted mRNA and the same approach could be employed for the screening of therapeutic candidates to regulate specific target proteins in diverse diseases.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , MicroARNs/análisis , Neoplasias/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Biología Computacional , Reparación del ADN/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Ensayos de Selección de Medicamentos Antitumorales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , Neoplasias/genética , Oligonucleótidos/genética , Oligonucleótidos/farmacología
15.
Sci Rep ; 10(1): 911, 2020 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-31969575

RESUMEN

The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (GaM; n = 19) and 19 untreated controls was performed. Treatment with MaR, but not GaM, significantly decreased fecal microbiota abundance and diversity, and expanded the abundance and diversity of antimicrobial resistance genes in feces. Soil plots experimentally infected with Rhodococcus equi (R. equi) and treated with MaR selected for MaR-resistant R. equi, whereas MaR-susceptible R. equi out-competed resistant isolates in GaM-treated or untreated plots. Our results indicate that MaR use promotes multi-drug resistance in R. equi and commensals that are shed into their environment where they can persist and potentially infect or colonize horses and other animals.


Asunto(s)
Antibacterianos/efectos adversos , Antibacterianos/farmacología , Profilaxis Antibiótica , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Enfermedades de los Caballos/prevención & control , Macrólidos/efectos adversos , Macrólidos/uso terapéutico , Compuestos Organometálicos/efectos adversos , Compuestos Organometálicos/uso terapéutico , Neumonía Bacteriana/prevención & control , Neumonía Bacteriana/veterinaria , Pironas/efectos adversos , Pironas/uso terapéutico , Rhodococcus equi/efectos de los fármacos , Rifampin/efectos adversos , Rifampin/uso terapéutico , Animales , Antibacterianos/uso terapéutico , Heces/microbiología , Caballos , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Compuestos Organometálicos/farmacología , Neumonía Bacteriana/microbiología , Pironas/farmacología , Rhodococcus equi/genética , Rifampin/farmacología
16.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-31979415

RESUMEN

ABCG2 is one of a triumvirate of human multidrug ATP binding cassette (ABC) transporters that are implicated in the defense of cells and tissues against cytotoxic chemicals, but these transporters can also confer chemotherapy resistance states in oncology. Understanding the mechanism of ABCG2 is thus imperative if we are to be able to counter its deleterious activity. The structure of ABCG2 and its related family members (ABCG5/G8) demonstrated that there were two interfaces between the nucleotide binding domains (NBD). In addition to the canonical ATP "sandwich-dimer" interface, there was a second contact region between residues at the C-terminus of the NBD. We investigated this second interface by making mutations to a series of residues that are in close interaction with the opposite NBD. Mutated ABCG2 isoforms were expressed in human embryonic kidney (HEK) 293T cells and analysed for targeting to the membrane, drug transport, and ATPase activity. Mutations to this second interface had a number of effects on ABCG2, including altered drug specificity, altered drug transport, and, in two mutants, a loss of ATPase activity. The results demonstrate that this region is particularly sensitive to mutation and can impact not only direct, local NBD events (i.e., ATP hydrolysis) but also the allosteric communication to the transmembrane domains and drug transport.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/química , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Adenosina Trifosfato/metabolismo , Preparaciones Farmacéuticas/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Adenosina Trifosfatasas/antagonistas & inhibidores , Adenosina Trifosfatasas/metabolismo , Animales , Transporte Biológico/genética , Embrión de Pollo , Clorofila/análogos & derivados , Clorofila/metabolismo , Resistencia a Múltiples Medicamentos/genética , Células HEK293 , Humanos , Hidrólisis , Mitoxantrona/metabolismo , Mutación , Dominios Proteicos/genética , Inhibidores de Topoisomerasa II/metabolismo
17.
Sci Rep ; 10(1): 1232, 2020 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988374

RESUMEN

Antibiotic-resistant Klebsiella pneumoniae is increasingly being implicated in invasive infections worldwide with high mortalities. Forty-two multidrug resistant (MDR) K. pneumoniae isolates were collected over a 4-month period. Antimicrobial susceptibility was determined using Microscan. The evolutionary epidemiology, resistome, virulome and mobilome of the isolates were characterised using whole-genome sequencing and bioinformatics analysis. All isolates contained the blaCTX-M gene, whilst 41/42(97%) contained blaTEM, 36/42(86%) contained blaOXA and 35/42(83%) harboured blaSHV genes. Other resistance genes found included blaLEN, aac(6')-lb-cr, qnrA, qnrB, qnrS, oqxAB, aad, aph, dfr, sul1, sul2, fosA, and cat genes. Fluoroquinolone and colistin resistance-conferring mutations in parC, gyrAB, pmrAB, phoPQ and kpnEF were identified. The blaLEN gene, rarely described worldwide, was identified in four isolates. The isolates comprised diverse sequence types, the most common being ST152 in 7/42(17%) isolates; clone-specific O and K capsule types were identified. Diverse virulence genes that were not clone-specific were identified in all but one isolate. IncF, IncH and IncI plasmid replicons and two novel integrons were present. The blaCTX-M-15 and blaTEM-1 genes were bracketed by Tn3 transposons, ISEc9, a resolvase and IS91 insertion sequence. There were 20 gene cassettes in 14 different cassette arrays, with the dfrA and aadA gene cassettes being the most frequent. Phylogenetic analysis demonstrated that the isolates were evolutionarily associated with strains from both South Africa and abroad. These findings depict the rich resistome, mobilome and virulome repertoire in clinical K. pneumoniae strains, which are mainly transmitted by clonal, multiclonal and horizontal means in South Africa.


Asunto(s)
Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Resistencia a Múltiples Medicamentos/genética , Farmacorresistencia Bacteriana Múltiple/genética , Evolución Molecular , Genes Bacterianos/genética , Genotipo , Klebsiella pneumoniae/aislamiento & purificación , Epidemiología Molecular/métodos , Neumonía Bacteriana/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Sudáfrica
18.
Cells ; 9(2)2020 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-31991926

RESUMEN

: The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 ABC transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in ABCC1, but not in the other ABC transporters investigated. Diverse ABCC1 mutations were found, including nonsense mutations causing premature stop codons, and compared with the wild-type protein in terms of their protein structure. Nonsense mutations lead to truncated protein structures. Molecular docking and heat map analyses of ABCC1/MRP1 pointed out that Lys498* appeared in a separate cluster branch due to the large deletion, leading to a massive disruption in the protein conformation. The resulting proteins, which are nonfunctional due to nonsense mutations in tumors, offer a promising chemotherapy strategy since tumors with nonsense mutations may be more sensitive to anticancer drugs than wild-type ABCC1-expressing tumors. This could provide a novel tumor-specific toxicity strategy and a way to overcome drug resistance.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Neoplasias/genética , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/metabolismo , Codón sin Sentido , Femenino , Humanos , Masculino , Simulación del Acoplamiento Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/química , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Neoplasias/metabolismo , Polimorfismo de Nucleótido Simple
19.
Aquat Toxicol ; 218: 105333, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31783301

RESUMEN

In the current study, to investigate the effect of imidacloprid on benthic bivalves, adult Asian clams (Corbicula fluminea) were exposed to 0, 20, 200, and 2000 µg/L imidacloprid for 30 d. Imidacloprid significantly inhibited the siphoning and burrowing behaviour (p < 0.05) of the clams. Significant histopathological changes were associated with degeneration of the cilium, the contraction and adhesion of the lymphocyte, and the swelling of epithelium cells in gills, and there was notable degeneration in the digestive tubules, haemolytic infiltration in the connective tissue and epithelial cell necrosis in the digestive glands in the 2000 µg/L treatment group. The activity of AChE in the digestive glands was significantly inhibited at all treatment levels, whereas this inhibition was observed in gills only in the 2000 µg/L treatment (p < 0.05). Additionally, indicators of the antioxidant system (e.g., SOD, CAT, and GST activity) and MDA content were significantly increased in the gills and digestive glands with all treatments (p < 0.05). Moreover, the mRNA expression levels of Hsp genes (hsp 22, hsp 40, hsp 60, hsp 70, hsp 90) and multixenobiotic resistance (MXR) system-related genes (abcb1, abcc1) were significantly downregulated (p < 0.05). Therefore, our results suggest that imidacloprid changes the oxidative stress, cellular detoxification, and MXR system of C. fluminea. Our findings provide new insights into the effects of neonicotinoids on benthic bivalves such as C. fluminea.


Asunto(s)
Antioxidantes/metabolismo , Corbicula/efectos de los fármacos , Resistencia a Múltiples Medicamentos , Neonicotinoides/toxicidad , Nitrocompuestos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Xenobióticos/toxicidad , Animales , Corbicula/genética , Corbicula/metabolismo , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos/genética , Agua Dulce/química , Branquias/efectos de los fármacos , Branquias/metabolismo , Branquias/patología , Estrés Oxidativo/efectos de los fármacos
20.
Arch Virol ; 165(2): 387-396, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31865470

RESUMEN

A pathogen of significance in the aquaculture sector, the Gram-negative marine bacterium Vibrio parahaemolyticus causes gastroenteritis associated with consumption of improperly prepared seafood. This bacterium can be controlled using lytic bacteriophages as an alternative to antibiotics. Ï•VP-1 is a lytic phage of V. parahaemolyticus that was isolated from an aquafarm water sample with the aim of assessing its potential as a bio-control agent and determining its physicochemical properties and genomic sequence. Morphological analysis by transmission electron microscopy and phylogenetic analysis based on the large terminase subunit gene showed that this phage belongs to the family Myoviridae. It could infect multiple-drug-resistant (MDR) V. parahaemolyticus and V. alginolyticus strains of mangrove and seafood origin. With a maximum adsorption time of 30 min, ϕVP-1 has a short latent period of 10 min with burst size of 44 particles/cell. Whole-genome sequencing was done using the Illumina platform, and annotation was done using GeneMarkS and Prodigal. The 150,764bp genome with an overall G+C content of 41.84% had 203 putative protein-encoding open reading frames, one tRNA gene, and 66 predicted promoters. A number of putative DNA replication and regulation, DNA packaging and structure, and host lysis genes were identified. Comparison of the ϕVP-1 genome sequence to those of known Vibrio phages indicated little discernible DNA sequence similarity, suggesting that ϕVP-1 is a novel Vibrio phage. Sequence analysis revealed the presence of 64 potential ORFs with a T4-like genomic organization. In silico analysis suggested an obligate lytic life cycle and showed the absence of lysogeny or virulence genes. The complete sequence of Ï•VP-1 was annotated and deposited in the GenBank database (accession no. MH363700). The genetic features of this novel phage suggest that it might be applicable for phage therapy against pathogenic strains of V. parahaemolyticus.


Asunto(s)
Bacteriófagos/genética , Resistencia a Múltiples Medicamentos/genética , Genoma Viral/genética , Myoviridae/genética , Vibrio parahaemolyticus/virología , Acuicultura/métodos , Composición de Base/genética , Biopelículas , Genómica/métodos , Sistemas de Lectura Abierta/genética , Terapia de Fagos/métodos , Filogenia
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