| 1. |
- El Zowalaty, Mohamed E., et al.
(författare)
-
Genome sequences of two multidrug-resistant Escherichia coli strains MEZEC8 and MEZEC10 isolated from livestock in South Africa
- 2020
-
Ingår i: Journal of Global Antimicrobial Resistance. - OXFORD ENGLAND : Elsevier BV. - 2213-7165 .- 2213-7173. ; 23, s. 445-449
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The emergence of antimicrobial-resistant livestock-associated Escherichia coli represents a great public health concern. Here we report the draft genome sequences of two multidrug-resistant livestock-associated E. coli strains MEZEC8 and MEZEC10 isolated from sheep in South Africa. Methods: Genomic DNA of E. coli strains MEZEC8 and MEZEC10 was sequenced using an Illumina MiSeq platform. Generated reads were trimmed and de novo assembled. The assembled contigs were analysed for antimicrobial resistance genes, chromosomal mutations and extrachromosomal plasmids, and the sequence type (ST) was determined by multilocus sequence typing (MLST). To compare strains MEZEC8 and MEZEC10 with other previously published sequences of E. coli strains, raw read sequences of E. coli from livestock were downloaded from the NCBI's Sequence Read Archive and all sequence files were treated identically to generate a core genome bootstrapped maximum likelihood phylogenetic tree. Results: Antimicrobial resistance genes were detected in MEZEC8 and MEZEC10 conferring resistance to tetracycline and macrolides. MEZEC10 harboured two extrachromosomal plasmids (pO111 and Incl2), while MEZEC8 did not contain any extrachromosomal plasmids. Strain MEZEC8 belonged to serotype H25:O9 and ST58, whereas strain MEZEC10 belonged to serotype H49:O8 and ST1844. Conclusion: The genome sequences of E. coli strains MEZEC8 and MEZEC10 will serve as a reference point for molecular epidemiological studies of antimicrobial-resistant livestock-associated E. coli in Africa. In addition, this study allows in-depth analysis of genomic structure and will provide valuable information enabling us understand the antimicrobial resistance of livestock-associated E. coli. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
|
|
| 2. |
- El Zowalaty, Mohamed E., et al.
(författare)
-
Genome sequences of two Salmonella enterica strains (MEZSAL74 and MEZSAL81) harbouring multiple antimicrobial resistance genes isolated from livestock in South Africa
- 2020
-
Ingår i: Journal of Global Antimicrobial Resistance. - : Elsevier. - 2213-7165 .- 2213-7173. ; 21, s. 396-398
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Antimicrobial-resistant livestock-associated Salmonella enterica infections pose a significant public-health threat worldwide. Here we report for the first time the draft genome sequences of two multidrug-resistant livestock-associated S. enterica strains isolated from a chicken and a cow in South Africa. Methods: Genomic DNA of S. enterica strains MEZSAL74 and MEZSAL81 was sequenced using an Illumina MiSeq platform. The generated reads were trimmed and de novo assembled. The assembled contigs were analysed for antimicrobial resistance genes, chromosomal mutations and extrachromosomal plasmids. Multilocus sequence typing (MLST) was also performed. In order to compare isolates MEZSAL74 and MEZSAL81 with other previously sequenced S. enterica isolates, raw read sequences were downloaded and all sequence files were treated identically to generate a bootstrapped maximum likelihood phylogenetic tree. Results: Extrachromosomal plasmids and genetic determinants of antimicrobial resistance were detected in both sequenced bacterial isolates to aminoglycosides and fluoroquinolones. By MLST, strain MEZSAL74 belonged to an unknown sequence type (ST) and strain MEZSAL81 belonged to ST33. Conclusion: The genome sequences of strains MEZSAL74 and MEZSAL81 reported here will serve as a reference for molecular epidemiological studies of antimicrobial-resistant livestock-associated S. enterica in Africa. (c) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
|
|
| 3. |
- Abouelela, M. E., et al.
(författare)
-
Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development
- 2021
-
Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 26:6
-
Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.
|
|
| 4. |
- Adel, Amany, et al.
(författare)
-
Epidemiological and molecular analysis of circulating fowl adenoviruses and emerging of serotypes 1, 3, and 8b in Egypt
- 2021
-
Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 7:12
-
Tidskriftsartikel (refereegranskat)abstract
- Fowl adenoviruses (FAdVs) are a large group of viruses of different serotypes. They are responsible for inclusion body hepatitis, adenoviral gizzard erosion, and hepatitis hydropericardium syndrome. The present study presents a comprehensive overview of FAdVs in Egypt, with a focus on the epidemiological features of virus serotypes across the country. We conducted molecular investigation of multiple FAdV species based on the genetic signature of hypervariable regions 1-4 in the loop1 (L1) region of the hexon gene. Epidemiologically, the Nile Delta governorates showed high positivity of FAdVs, which were more commonly found in broilers than in layers. Genetically, species D and serotype 8a/E dominated, and the findings also revealed the emergence of new FAdV serotypes 1, 3, and 8b. The comparative analysis of hypervariable regions in the L1 region of the hexon gene revealed variables specific to each virus serotype. In silico predictions of L1 region revealed variations in the molecular structure and predicted the antigenic epitopes which may affect the cross-antigenicity between the different FAdV species and serotypes.
|
|
| 5. |
- Hamed, A. N. E., et al.
(författare)
-
Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking
- 2022
-
Ingår i: Rsc Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 12:15, s. 9154-9162
-
Tidskriftsartikel (refereegranskat)abstract
- The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3-O-neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3-O-beta-D-gluacopyranoside (9). The compounds 2, 3, 5-7 and 9 were isolated for the first time from the genus Carica. An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and ditorin demonstrated the most potent cytotoxic activities with an IC50 of 1.11 +/- 0.06 and 2.47 +/- 0.14 mu M, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR(wt) kinase inhibition activities with an IC50 of 37.3 +/- 1.9 and 41.08 +/- 2.1 nM, respectively, compared with the positive control erlotinib (IC50 = 35.94 +/- 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC50 of 77.41 +/- 4.53 and 92.84 +/- 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC50 = 77.72 +/- 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of -4.5287 kcal mol(-1) and RMSD value of 1.69 angstrom. Ditorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of -14.2074 and RMSD value of 1.56 angstrom. Compounds (1-3) possessed a good bioavallability score with a 0.55 value.
|
|
| 6. |
- El-Helbawy, N. F., et al.
(författare)
-
Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma
- 2022
-
Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3037 .- 1467-3045. ; 44:9, s. 4118-4131
-
Tidskriftsartikel (refereegranskat)abstract
- Melanoma is a lethal form of skin cancer. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment; however, drug resistance is rapidly acquired. Several studies have reported an increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, the bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identifies the significant upregulation of extra-cellular matrix and cellular adhesion genes in young cohorts, while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 are significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration are differentially expressed. The differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism is also observed. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes in melanoma, and novel therapeutic targets for future studies. © 2022 by the authors.
|
|
| 7. |
- Hassan, Ayah M., et al.
(författare)
-
Molecular detection, phylogenetic analysis and genetic diversity of recently isolated foot-and-mouth disease virus serotype A African topotype, Genotype IV
- 2022
-
Ingår i: Virology Journal. - : BioMed Central (BMC). - 1743-422X. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurveillance for circulating emerging diseases of economic importance has a major role in the rapid response to major pathogen outbreaks. Foot-and-mouth disease virus (FMDV) is one of the significant endemic viruses in Egypt. FMDV is periodically investigated for monitoring evolution and emergence of new variants. The genetic characterization of foot-and-mouth disease (FMD) virus serotype A responsible for recent outbreaks of FMD in Egypt was determined.MethodsSamples were collected from different locations and virus isolation was performed using BHK-21 cells. Viral RNA was extracted and samples were screened for FMDV using real-time RT-PCR. DNA sequence analysis was performed and computational and bioinformatics analyses were used to determine the substitution rates and phylogenetic relationship.ResultsSequence and phylogenetic analyses of full-length 1D region of FMDV samples collected from different governorates in 2020 showed close similarity to Egyptian FMDV strains from serotype A-African topotype-G-IV with genetic variation of 6.5%. Recently isolated FMDV strains showed high genetic variations from locally used vaccine strains in the major antigenic sites of VP1 region.ConclusionsAlthough, efforts made by the veterinary authorities to implement an effective mass vaccination plan, the recently detected FMDV strains in this study could not be subtyped using the FMDV primers routinely used for molecular serotyping. These dissimilarities raise the alarm for reconsideration of the FMDV isolates used in vaccine manufacture. Clearly close monitoring of FMD in Egypt is urgently required to define the risks of future outbreaks and to ensure appropriate control measures against FMD major outbreaks.
|
|
| 8. |
- Uddin, Md Bashir, et al.
(författare)
-
Multidrug Antimicrobial Resistance and Molecular Detection of mcr-1 Gene in Salmonella Species Isolated from Chicken
- 2021
-
Ingår i: Animals. - : MDPI. - 2076-2615. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Colistin (polymyxin E) is widely used in animal and human medicine and is increasingly used as one of the last-resort antibiotics against Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant Gram-negative bacteria, resistance to this antibiotic ought to be monitored. The study was undertaken to elucidate the molecular mechanisms, genetic relationships and phenotype correlations of colistin-resistant isolates. Here, we report the detection of the mcr-1 gene in chicken-associated Salmonella isolates in Bangladesh and its in-silico functional analysis. Out of 100 samples, 82 Salmonella spp. were isolated from chicken specimens (liver, intestine). Phenotypic disc diffusion and minimum inhibitory concentration (MIC) assay using different antimicrobial agents were performed. Salmonella isolates were characterized using PCR methods targeting genus-specific invA and mcr-1 genes with validation for the functional analysis. The majority of the tested Salmonella isolates were found resistant to colistin (92.68%), ciprofloxacin (73.17%), tigecycline (62.20%) and trimethoprim/sulfamethoxazole (60.98%). When screened using PCR, five out of ten Salmonella isolates were found to carry the mcr-1 gene. One isolate was confirmed for Salmonella enterica subsp. enterica serovar Enteritidis, and other four isolates were confirmed for Salmonella enterica subsp. enterica serovar Typhimurium. Sequencing and phylogenetic analysis revealed a divergent evolutionary relationship between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, rendering them resistant to colistin. Three-dimensional homology structural analysis of MCR-1 proteins and molecular docking interactions suggested that MCR-1 and LptA share a similar substrate binding cavity, which could be validated for the functional analysis. The comprehensive molecular and in-silico analyses of the colistin resistance mcr-1 gene of Salmonella spp. of chicken origin in the present study highlight the importance of continued monitoring and surveillance for antimicrobial resistance among pathogens in food chain animals.
|
|
| 9. |
- Malik, Yashpal S., et al.
(författare)
-
SARS-CoV-2 Spike Protein Extrapolation for COVID Diagnosis and Vaccine Development
- 2021
-
Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 8
-
Forskningsöversikt (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to coronavirus disease 2019 (COVID-19) pandemic affecting nearly 71.2 million humans in more than 191 countries, with more than 1.6 million mortalities as of 12 December, 2020. The spike glycoprotein (S-protein), anchored onto the virus envelope, is the trimer of S-protein comprised of S1 and S2 domains which interacts with host cell receptors and facilitates virus-cell membrane fusion. The S1 domain comprises of a receptor binding domain (RBD) possessing an N-terminal domain and two subdomains (SD1 and SD2). Certain regions of S-protein of SARS-CoV-2 such as S2 domain and fragment of the RBD remain conserved despite the high selection pressure. These conserved regions of the S-protein are extrapolated as the potential target for developing molecular diagnostic techniques. Further, the S-protein acts as an antigenic target for different serological assay platforms for the diagnosis of COVID-19. Virus-specific IgM and IgG antibodies can be used to detect viral proteins in ELISA and lateral flow immunoassays. The S-protein of SARS-CoV-2 has very high sequence similarity to SARS-CoV-1, and the monoclonal antibodies (mAbs) against SARS-CoV-1 cross-react with S-protein of SARS-CoV-2 and neutralize its activity. Furthermore, in vitro studies have demonstrated that polyclonal antibodies targeted against the RBD of S-protein of SARS-CoV-1 can neutralize SARS-CoV-2 thus inhibiting its infectivity in permissive cell lines. Research on coronaviral S-proteins paves the way for the development of vaccines that may prevent SARS-CoV-2 infection and alleviate the current global coronavirus pandemic. However, specific neutralizing mAbs against SARS-CoV-2 are in clinical development. Therefore, neutralizing antibodies targeting SARS-CoV-2 S-protein are promising specific antiviral therapeutics for pre-and post-exposure prophylaxis and treatment of SARS-CoV-2 infection. We hereby review the approaches taken by researchers across the world to use spike gene and S-glycoprotein for the development of effective diagnostics, vaccines and therapeutics against SARA-CoV-2 infection the COVID-19 pandemic.
|
|
| 10. |
- Malmhäll-Bah, Eric, et al.
(författare)
-
Rho-GTPase dependent leukocyte interaction generates pro-inflammatory thymic Tregs and causes arthritis
- 2022
-
Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 130
-
Tidskriftsartikel (refereegranskat)abstract
- Conditional mutation of protein geranylgeranyltransferase type I (GGTase-I) in macrophages (GLC) activates Rho-GTPases and causes arthritis in mice. Knocking out Rag1 in GLC mice alleviates arthritis which indicates that lymphocytes are required for arthritis development in those mice. To study GLC dependent changes in the adaptive immunity, we isolated CD4(+) T cells from GLC mice (CD4(+)GLCs). Spleen and joint draining lymph nodes (dLN) CD4(+)GLCs exhibited high expression of Cdc42 and Rac1, which repressed the caudal HOXA proteins and activated the mechanosensory complex to facilitate migration. These CDC42/RAC1 rich CD4(+)GLCs presented a complete signature of GARP(+)NRP1(+)IKZF2(+)FOXP3(+) regulatory T cells (Tregs) of thymic origin. Activation of the beta-catenin/Lef1 axis promoted a pro-inflammatory Th1 phenotype of Tregs, which was strongly associated with arthritis severity. Knockout of Cdc42 in macrophages of GLC mice affected CD4(+) cell biology and triggered development of non-thymic Tregs. Knockout of Rac1 and RhoA had no such effects on CD4(+) cells although it alleviated arthritis in GLC mice. Disrupting macrophage and T cell interaction with CTLA4 fusion protein reduced the Th1-driven inflammation and enrichment of thymic Tregs into dLNs. Antigen challenge reinforced the CD4(+)GLC phenotype in non-arthritic heterozygote GLC mice and increased accumulation of Rho-GTPase expressing thymic Tregs in dLNs. Our study demonstrates an unexpected role of macrophages in stimulating the development of pro-inflammatory thymic Tregs and reveal activation of Rho-GTPases behind their arthri-togenic phenotype.
|
|
| 11. |
- Uddin, Md Bashir, et al.
(författare)
-
Molecular Detection of Colistin Resistance mcr-1 Gene in Multidrug-Resistant Escherichia coli Isolated from Chicken
- 2022
-
Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Zoonotic and antimicrobial-resistant Escherichia coli (hereafter, E. coli) is a global public health threat which can lead to detrimental effects on human health. Here, we aim to investigate the antimicrobial resistance and the presence of mcr-1 gene in E. coli isolated from chicken feces. Ninety-four E. coli isolates were obtained from samples collected from different locations in Bangladesh, and the isolates were identified using conventional microbiological tests. Phenotypic disk diffusion tests using 20 antimicrobial agents were performed according to CLSI-EUCAST guidelines, and minimum inhibitory concentrations (MICs) were determined for a subset of samples. E. coli isolates showed high resistance to colistin (88.30%), ciprofloxacin (77.66%), trimethoprim/sulfamethoxazole (76.60%), tigecycline (75.53%), and enrofloxacin (71.28%). Additionally, the pathotype eaeA gene was confirmed in ten randomly selected E. coli isolates using primer-specific polymerase chain reaction (PCR). The presence of mcr-1 gene was confirmed using PCR and sequencing analysis in six out of ten E. coli isolates. Furthermore, sequencing and phylogenetic analyses revealed a similarity between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, indicating that the six tested isolates were colistin resistant. Finally, the findings of the present study showed that E. coli isolated from chicken harbored mcr-1 gene, and multidrug and colistin resistance. These findings accentuate the need to implement strict measures to limit the imprudent use of antibiotics, particularly colistin, in agriculture and poultry farms.
|
|
| 12. |
- Zou, Zhiyuan V., et al.
(författare)
-
Antioxidants promote intestinal tumor progression in mice.
- 2021
-
Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 10:2
-
Tidskriftsartikel (refereegranskat)abstract
- Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.
|
|
