14 results on '"Awolope A"'
Search Results
2. Genome-guided bioprospecting for novel antibiotic lead compounds
- Author
-
Awolope, Opeyemi K., Lamb, A., O'Driscoll, N., and di Salvo, A.
- Subjects
Beta-Lactone natural compounds ,ß-Lactone natural compounds ,Genome mining ,Bioprospecting ,Antibiotic lead compounds ,Antimicrobial resistance ,Antibiotics - Abstract
Antimicrobial resistance continues to pose a threat to health and wellbeing. Unmitigated, it is predicted to be the leading cause of death by 2050. Hence, the sustained development of novel antibiotics is crucial. As over 60% of licensed antibiotics are based on scaffolds derived from less than 1% of all known bacterial species, bacterial secondary metabolites constitute an untapped source of novel antibiotics. The aim of this project therefore was to expand the chemical space of bacteria-derived antibiotic lead compounds, using genomics approach. To that end, a topsoil sample was collected from the rhizosphere in which antibiosis occurs naturally. Using starvation stress, sixty-five isolates were recovered from the sample, out of which four were selected based on morphology and designated A13BB, A23BA, A13AA and A23AA. A13BB was identified by 16S rRNA gene sequence comparison as a Pseudomonas spp. and the other three isolates as Hafnia/Obesumbacterium spp. A database search showed that species belonging to these genera have genomes larger than the 3 Mb size above which an increasing proportion of a bacterial genome is dedicated to secondary metabolism. Given their ecological origin, expected genome size and ability to withstand starvation stress, these four isolates were presumed to harbour antibiotic-encoding gene clusters. Isolates A13BB and A23BA were therefore selected for genome mining in the first instance. Illumina and GridION/MinION sequencing data were obtained for both isolates and assembled into high-quality genomes. Isolates' identities were confirmed by FastANI analysis as strains of P. fragi and H. alvei, with 4.94 and 4.77 Mb genomes, respectively. Assembled genomes were mined with antiSMASH. Amongst other secondary metabolite biosynthetic gene clusters (smBGCs) detected, the β-lactone smBGCs in both genomes were selected for activation as their end products bear the hallmarks of an 'ideal antibiotic' that can inhibit several bacteria-specific enzymes simultaneously. Analysis of these smBGCs revealed genes encoding two core enzymes: 2-isopropylmalate synthase (2-IPMS) and acyl CoA ligase homologues. In the biosynthetic pathway, 2-IPMS catalyses the condensation of acetyl CoA with the degradation product of valine or isoleucine to form 2-IPM. 2-IPM is isomerised to 3-IPM which then forms the β-lactone warhead through reactions catalysed by acyl CoA ligase. It was speculated that the β-lactone compound is biosynthesised to efficiently rid the organism of potentially harmful metabolic intermediates as it grows on poor carbon and nitrogen sources. Strain fermentation was therefore performed with 10.8 mM acetate as the main carbon source, and 5 mM L-valine or L-isoleucine as the nitrogen source. Fermentation extracts were analysed by LC-MS with at least thirty-seven metabolite ions detected. Many of these ions have masses in the range m/z 230-750, which is an ideal mass range for antibiotic molecules. As β-lactone compounds are difficult to identify in crude extracts, especially when utilising single-stage mass spectrometry, reactivity-guided screening of extracts with cysteine thiol probe was performed as the probe forms UV- and MS-visible adducts with β-lactone compounds. However, complete dimerization of probe at a faster-than-expected rate in extract matrices hindered successful screening. This meant that it was not possible to determine if any crude extract components were β-lactone compounds without further analysis. Measures to limit or eliminate probe dimerization are proposed, together with molecular networking strategies that can afford global visualisation and rapid dereplication of extract components, using tandem mass spectrometry fragmentation patterns of parent ions. This project provides an original and robust workflow that serves as a strong starting point in the isolation of novel β-lactone compounds from crude extracts, followed by structural optimisation and bioactivity profiling. The hitherto unrecognised potential of β-lactone natural compounds as 'ideal antibiotics' is highlighted, and several structural optimisation strategies required to harness this potential are proposed. The genomes assembled here, and associated data have been deposited in the repositories of the International Nucleotide Sequence Database Collaboration for repurposing by other researchers. Likewise, the hidden metabolic and biosynthetic potentials of P. fragi and H. alvei species uncovered by RASTtk and antiSMASH analyses have been catalogued and placed in the public domain, with many of these attributes reported for the first time.
- Published
- 2023
3. 279 Electronic Health Record Data and Topological Data Analysis to Predict Clinical Outcomes Post Myocardial Infarction
- Author
-
Anna Awolope, Esha Datta, Aditya Ballal, Leighton T Izu, and Javier E. López
- Subjects
Medicine - Abstract
OBJECTIVES/GOALS: The aim of this study is to analyze electronic health record (EHR) data using Mapper PLUS (MP), a new mathematical model, to classify acute myocardial infarction (MI) patients by risk of major adverse events (AE). We tested MP’s ability to define patient subgroups with distinctive risk for death, heart failure or recurrent MI after revascularization. METHODS/STUDY POPULATION: An EHR retrospective analysis of 797 MI patients and 29 variables (i.e., laboratory tests, imaging, vitals, and clinical traits) collected at the time of hospitalization was conducted. All patients received percutaneous coronary intervention and standard pharmacotherapy. MP analysis produced a multi-dimensional nodal graph of the patients based on similarities found within variables. Two algorithms, Walk Likelihood and Walk Likelihood Community Finder were applied to the graph which formed joint clusters according to spatial distance within nodes. The final output was three clusters for risk level evaluation. Risk level (low vs. high) was relative to the average risk of AEs for the entire cohort one year post MI. RESULTS/ANTICIPATED RESULTS: Of three patient subgroups, one (n= 318) had a >1 fold change for the probability of survival without AE when compared to the overall cohort and thus was defined as the low-risk group. The second group (n=304) had DISCUSSION/SIGNIFICANCE: MP stratifies patients into three groups according to predictive variables which relate to the risk for AE following an acute MI treatment. This is a new topological method for patient classification based on minimal input strictly from pre-collected EHR data. More cohort studies are needed to validate MP to classify patients for precision medicine.
- Published
- 2023
- Full Text
- View/download PDF
4. The complete genome sequence of Hafnia alvei A23BA; a potential antibiotic-producing rhizobacterium
- Author
-
Opeyemi K. Awolope, Noelle H. O’Driscoll, Alberto Di Salvo, and Andrew J. Lamb
- Subjects
Hafnia alvei ,H. alvei ,Genome mining ,Biosynthetic gene clusters ,Antibiotics ,Rhizobacteria ,Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Objectives The urgent need for novel antibiotics cannot be overemphasized. Hafnia alvei A23BA was isolated from plant rhizosphere as part of an effort to recover novel antibiotic-producing bacterial strains from soil samples. The genome of the isolate was sequenced to facilitate mining for potential antibiotic-encoding biosynthetic gene clusters and to gain insights into how these gene clusters could be activated. Data description Here, we report the complete genome sequence of H. alvei A23BA obtained from the hybrid assembly of Illumina HiSeq and GridION reads. The genome, consisting of a circular chromosome and a circular plasmid, is 4.77 Mb in size with a GC content of 48.77%. The assembly is 99.5% complete with genomic features including 4,217 CDSs, 125 RNAs, and 30 pseudogenes. Thiopeptide, beta-lactone, siderophore, and homoserine lactone biosynthetic gene clusters were also identified. Other gene clusters of interest include those associated with bioremediation, biocontrol, and plant growth promotion- all of which are reported for H. alvei for the first time. This dataset serves to expedite the exploration of the biosynthetic and metabolic potentials of the species. Furthermore, being the first published genome sequence of a soil isolate, this dataset enriches the comparative genomics study of H. alvei strains.
- Published
- 2021
- Full Text
- View/download PDF
5. Quercetin Zinc and Iron Metal Complexes Protect against Sodium Arsenite Intoxication in the Hepato-Renal System of Wistar Rats via the Oxidative Stress Pathway
- Author
-
Oluwatoyin O. Ojo, Deborah I. Fatokun, Ikechukwu P. Ejidike, Rachel U. Awolope, and Saheed O. Sanni
- Subjects
Toxicology. Poisons ,RA1190-1270 - Abstract
Background. Chronic exposure to arsenic is a major health concern consequent upon generation of excessive reactive oxygen species. The safety of treatment with chelating agents has not been well established; therefore, there is a need for a paradigm shift in the approach to management of arsenic toxicity. Bioflavonoids are known to influence redox homeostasis in cells; the study therefore investigates the efficacy of quercetin and its zinc and iron metal complexes on sodium arsenite (NaAr)-intoxication in rats. Methods. Spectroscopic study of quercetin hydrate and its metal complexes was performed using UV-Vis and FT-IR spectrometer. Furthermore, twenty male Wistar rats were obtained and equally divided into four groups, treated orally and daily for 28 days with 10 mg/kg NaAr, 30 mg/kg quercetin, quercetin-zinc, and quercetin-iron separately. Five more rats were used as control. Plasmatic aspartate transferase (AST), alanine transferase (ALT), creatinine (CREA), and total protein (TP) were estimated. Levels of kidney and liver lipid peroxidation (LPO), glutathione (GSH), catalase (CAT), and glutathione-S-transferase (GST) were determined. Histology was used to view the lesions. Results. Treatment of arsenic-toxicity with quercetin and its complexes decreased the activities of ALT, AST, CREA, TP, CAT, and GST and concentration of LPO and GSH. Quercetin-zn treatment showed a better result than quercetin-iron in the liver. Histology results showed absence of lesions in quercetin zinc and iron treatment in both the kidney and the liver. Conclusion. Quercetin zinc and iron increased the bioavailability of quercetin and therefore could be relevant as adjuvants in arsenic poisoning.
- Published
- 2022
- Full Text
- View/download PDF
6. The complete genome sequence of Hafnia alvei A23BA; a potential antibiotic-producing rhizobacterium
- Author
-
Awolope, Opeyemi K., O’Driscoll, Noelle H., Di Salvo, Alberto, and Lamb, Andrew J.
- Published
- 2021
- Full Text
- View/download PDF
7. De novo genome assembly and analysis unveil biosynthetic and metabolic potentials of Pseudomonas fragi A13BB
- Author
-
Awolope, Opeyemi K., O’Driscoll, Noelle H., Di Salvo, Alberto, and Lamb, Andrew J.
- Published
- 2021
- Full Text
- View/download PDF
8. Genome-guided bioprospecting for novel antibiotic lead compounds
- Author
-
Awolope, Opeyemi
- Subjects
FOS: Biological sciences - Abstract
Antimicrobial resistance continues to pose a threat to health and wellbeing. Unmitigated, it is predicted to be the leading cause of death by 2050. Hence, the sustained development of novel antibiotics is crucial. As over 60% of licensed antibiotics are based on scaffolds derived from less than 1% of all known bacterial species, bacterial secondary metabolites constitute an untapped source of novel antibiotics. The aim of this project therefore was to expand the chemical space of bacteria-derived antibiotic lead compounds, using genomics approach. To that end, a topsoil sample was collected from the rhizosphere in which antibiosis occurs naturally. Using starvation stress, sixty-five isolates were recovered from the sample, out of which four were selected based on morphology and designated A13BB, A23BA, A13AA and A23AA. A13BB was identified by 16S rRNA gene sequence comparison as a Pseudomonas spp. and the other three isolates as Hafnia/Obesumbacterium spp. A database search showed that species belonging to these genera have genomes larger than the 3 Mb size above which an increasing proportion of a bacterial genome is dedicated to secondary metabolism. Given their ecological origin, expected genome size and ability to withstand starvation stress, these four isolates were presumed to harbour antibiotic-encoding gene clusters. Isolates A13BB and A23BA were therefore selected for genome mining in the first instance. Illumina and GridION/MinION sequencing data were obtained for both isolates and assembled into high-quality genomes. Isolates' identities were confirmed by FastANI analysis as strains of P. fragi and H. alvei, with 4.94 and 4.77 Mb genomes, respectively. Assembled genomes were mined with antiSMASH. Amongst other secondary metabolite biosynthetic gene clusters (smBGCs) detected, the β-lactone smBGCs in both genomes were selected for activation as their end products bear the hallmarks of an 'ideal antibiotic' that can inhibit several bacteria-specific enzymes simultaneously. Analysis of these smBGCs revealed genes encoding two core enzymes: 2-isopropylmalate synthase (2-IPMS) and acyl CoA ligase homologues. In the biosynthetic pathway, 2-IPMS catalyses the condensation of acetyl CoA with the degradation product of valine or isoleucine to form 2-IPM. 2-IPM is isomerised to 3-IPM which then forms the β-lactone warhead through reactions catalysed by acyl CoA ligase. It was speculated that the β-lactone compound is biosynthesised to efficiently rid the organism of potentially harmful metabolic intermediates as it grows on poor carbon and nitrogen sources. Strain fermentation was therefore performed with 10.8 mM acetate as the main carbon source, and 5 mM L-valine or L-isoleucine as the nitrogen source. Fermentation extracts were analysed by LC-MS with at least thirty-seven metabolite ions detected. Many of these ions have masses in the range m/z 230-750, which is an ideal mass range for antibiotic molecules. As β-lactone compounds are difficult to identify in crude extracts, especially when utilising single-stage mass spectrometry, reactivity-guided screening of extracts with cysteine thiol probe was performed as the probe forms UV- and MS-visible adducts with β-lactone compounds. However, complete dimerization of probe at a faster-than-expected rate in extract matrices hindered successful screening. This meant that it was not possible to determine if any crude extract components were β-lactone compounds without further analysis. Measures to limit or eliminate probe dimerization are proposed, together with molecular networking strategies that can afford global visualisation and rapid dereplication of extract components, using tandem mass spectrometry fragmentation patterns of parent ions. This project provides an original and robust workflow that serves as a strong starting point in the isolation of novel β-lactone compounds from crude extracts, followed by structural optimisation and bioactivity profiling. The hitherto unrecognised potential of β-lactone natural compounds as 'ideal antibiotics' is highlighted, and several structural optimisation strategies required to harness this potential are proposed. The genomes assembled here, and associated data have been deposited in the repositories of the International Nucleotide Sequence Database Collaboration for repurposing by other researchers. Likewise, the hidden metabolic and biosynthetic potentials of P. fragi and H. alvei species uncovered by RASTtk and antiSMASH analyses have been catalogued and placed in the public domain, with many of these attributes reported for the first time.
- Published
- 2023
- Full Text
- View/download PDF
9. Characterization and Photophysical Properties of Phthalocyanine-Cytidine-Single Walled Carbon Nanotube Anti-Cancer Complex
- Author
-
Awolope, R.O., Ejidike, I.P., and Nyokong, T.
- Abstract
Background: The mortality rate of cancer, one of the leading causes of death globally is continuously increasing. Despite the progress in preparing and approving conventional chemotherapeutic drugs, new forms of the diseases are evolving. Hence, an urgent need for alternative therapy .Objectives: To prepare combinatory drugs composed of nucleoside-metallophthalocyanine and a single-walled carbon complex as a potential anti-cancer agent.The complex is a major key player in photodynamic therapy. Cytidine, a nucleoside which is a major component of ribonucleic acid was chemically linked to zinc tetra-phenoxycarboxy phthalocyanine (1), a photoactive compound represented as ZnTCPC-cytidine (2). Complex 2 was adsorbed on single-walled carbon nanotube (SWCNT) represented as ZnTCPC-cytidine-SWCNT (3).Methods: Complexes 1, 2 and 3 were characterized using UV-visible and Fourier transform infrared (FTIR) spectroscopy. The photophysical properties such as fluorescence quantum and triplet quantum yield were studied using fluorescence emission and laser flash spectroscopy respectively.Results: The absorption spectra show that complex 1, 2 and 3 have the characteristics Q-band of metallophthalocyanine compounds, the FTIR spectra also confirmed that the cytidine was chemically linked to ZnTCPC, while ZnTCPC-cytidine was successfully adsorbed on SWCNT through π-π stacking. The fluorescence quantum yields were 0.10, 0.098 and 0.130, while the triplet quantum yield was 0.49, 0.76 and 0.78 for complex 1, 2 and 3 respectively.Conclusions: The triplet quantum yield result showed that complexes 2 and 3 can generate high singlet oxygen, the cytotoxic agent responsible for the irreversible destruction of cancerous cells. Hence, these complexes would find application as potential anticancer drugs for photodynamic therapy. Keywords: Zinc tetra-phenoxycarboxy phthalocyanine, Single-walled carbon nanotubes, cytidine, fluorescence and triplet quantum yields
- Published
- 2022
10. Preparation, Characterization, and Antimicrobial Activities of Mixed Ibuprofen-Salicylic Acid Metal-Drug Complexes
- Author
-
Mercy O. Bamigboye, Ikechukwu P. Ejidike, Racheal O. Awolope, Joshua A. Obaleye, and Favour K. Ejimofor
- Subjects
Spectra studies ,Metal-drug complexes ,Ibuprofen ,Salicylic acid ,Antimicrobial activity - Abstract
Most variants of bacteria are resistant to traditional antibiotics which are organic. To overcome the growing infections, bacteria resistant infections, and multiple drug resistance (MDR) rates, transition metals with biological importance were coordinated to organic ligands (Ibuprofen and Salicylic acid) with anti-inflammatory properties. In this study, metal complexes of mixed Ibuprofen and Salicylic acid were prepared using a standard method to give of the type [M(Ibu)(Sal)X] (where M = Fe2+, Ni2+, Cu2+, and X = Cl2, Ibu = Ibuprofen, Sal = Salicylic acid). The complexes were characterized by UV-visible spectroscopy, conductivity measurements, melting points, FT-IR, and X-ray diffraction. The metal ions are coordinated to the ligands via the carboxylato oxygen donor atoms of both ligands. From the physicochemical data, the complexes are non-electrolytes. The XRD study suggested that the metal complexes possess a well-defined crystalline structure with average crystallite sizes of < 62 nm. Evaluations of the antimicrobial activities of the ligands and their complexes against gram-positive bacteria (S. aureus, B. subtilis, S. faecalis) and gram-negative bacteria (K. pneumonia, E. coli, and P. aeroginosa) via standard method were utilized to determine the zones of inhibition. The complexes exhibited a higher zone of inhibition, indicating higher antimicrobial activities when compared to the parent ligand. The results revealed that the metal-drug complexes are promising chemotherapeutic agents with wide spectrum of activities. Keywords: Metal-drug complexes; Ibuprofen; Spectra studies; Salicylic acid; Antimicrobial activity
- Published
- 2021
11. Quercetin Zinc and Iron Metal Complexes Protect against Sodium Arsenite Intoxication in the Hepato-Renal System of Wistar Rats via the Oxidative Stress Pathway.
- Author
-
Ojo, Oluwatoyin O., Fatokun, Deborah I., Ejidike, Ikechukwu P., Awolope, Rachel U., and Sanni, Saheed O.
- Subjects
QUERCETIN ,LABORATORY rats ,SODIUM arsenite ,METAL complexes ,OXIDATIVE stress ,ZINC - Abstract
Background. Chronic exposure to arsenic is a major health concern consequent upon generation of excessive reactive oxygen species. The safety of treatment with chelating agents has not been well established; therefore, there is a need for a paradigm shift in the approach to management of arsenic toxicity. Bioflavonoids are known to influence redox homeostasis in cells; the study therefore investigates the efficacy of quercetin and its zinc and iron metal complexes on sodium arsenite (NaAr)-intoxication in rats. Methods. Spectroscopic study of quercetin hydrate and its metal complexes was performed using UV-Vis and FT-IR spectrometer. Furthermore, twenty male Wistar rats were obtained and equally divided into four groups, treated orally and daily for 28 days with 10 mg/kg NaAr, 30 mg/kg quercetin, quercetin-zinc, and quercetin-iron separately. Five more rats were used as control. Plasmatic aspartate transferase (AST), alanine transferase (ALT), creatinine (CREA), and total protein (TP) were estimated. Levels of kidney and liver lipid peroxidation (LPO), glutathione (GSH), catalase (CAT), and glutathione-S-transferase (GST) were determined. Histology was used to view the lesions. Results. Treatment of arsenic-toxicity with quercetin and its complexes decreased the activities of ALT, AST, CREA, TP, CAT, and GST and concentration of LPO and GSH. Quercetin-zn treatment showed a better result than quercetin-iron in the liver. Histology results showed absence of lesions in quercetin zinc and iron treatment in both the kidney and the liver. Conclusion. Quercetin zinc and iron increased the bioavailability of quercetin and therefore could be relevant as adjuvants in arsenic poisoning. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Preparation, Characterization, and Antimicrobial Activities of Mixed Ibuprofen-Salicylic Acid Metal-Drug Complexes.
- Author
-
Bamigboye, Mercy O., Ejidike, Ikechukwu P., Awolope, Racheal O., Obaleye, Joshua A., and Ejimofor, Favour K.
- Subjects
ANTI-infective agents ,IBUPROFEN ,SALICYLIC acid ,CANCER chemotherapy ,LIGAND binding (Biochemistry) - Abstract
Most variants of bacteria are resistant to traditional antibiotics which are organic. To overcome the growing infections, bacteria resistant infections, and multiple drug resistance (MDR) rates, transition metals with biological importance were coordinated to organic ligands (Ibuprofen and Salicylic acid) with anti-inflammatory properties. In this study, metal complexes of mixed Ibuprofen and Salicylic acid were prepared using a standard method to give of the type [M(Ibu)(Sal)X] (where M = Fe
2+ , Ni2+ , Cu2+ , and X = Cl2 , Ibu = Ibuprofen, Sal = Salicylic acid). The complexes were characterized by UV-visible spectroscopy, conductivity measurements, melting points, FT-IR, and X-ray diffraction. The metal ions are coordinated to the ligands via the carboxylato oxygen donor atoms of both ligands. From the physicochemical data, the complexes are non-electrolytes. The XRD study suggested that the metal complexes possess a well-defined crystalline structure with average crystallite sizes of < 62 nm. Evaluations of the antimicrobial activities of the ligands and their complexes against gram-positive bacteria (S. aureus, B. subtilis, S. faecalis) and gram-negative bacteria (K. pneumonia, E. coli, and P. aeroginosa) via standard method were utilized to determine the zones of inhibition. The complexes exhibited a higher zone of inhibition, indicating higher antimicrobial activities when compared to the parent ligand. The results revealed that the metal-drug complexes are promising chemotherapeutic agents with wide spectrum of activities. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
13. The construction and meaning of race within hypertension guidelines: a scoping review.
- Author
-
Razon, Na'amah, Gottlieb, Laura, Hahn, Monica, Jones, Danielle Hessler, El-Sabrout, Hannah, and Awolope, Anna
- Subjects
RACE ,RACISM in medicine ,ESSENTIAL hypertension ,HYPERTENSION ,RESEARCH personnel - Abstract
Context: Professional society guidelines are evidence-based recommendations intended to promote standardized care and improve health outcomes. In the context of increased recognition of the role racism has played in shaping medical practices, many healthcare researchers and practitioners have critiqued existing guidelines, particularly those that include race-based recommendations. These critiques question how implicit--and sometimes explicit--racism has influenced both the evidence that guidelines are based on and the interpretation of that evidence. Objective and study design: In this study, we conducted a scoping review of all professional guidelines focused on the treatment and management of essential hypertension published between 1977 and 2020 and examined how race and ethnicity influenced guideline recommendations. Results: We found that authors largely focused on Black and White categories, with few references to other groups. Guideline authors described race as a distinct, preestablished category with biological underpinnings (for example, recommended specific medication classes to a predefined racial group). No guideline discussed the history of racism and the role it has played in perpetuating hypertension (or other health) disparities or inequities. The characterizations of race in essential hypertension guidelines normalize race as a biological rather than social construct. Conclusion: As the health system grapples with how to address racism in medicine, exploring how professional care guidelines reflect an outdated understanding of race can help us understand both the social origins of and treatments for hypertension inequities. [ABSTRACT FROM AUTHOR]
- Published
- 2023
14. 279 Electronic Health Record Data and Topological Data Analysis to Predict Clinical Outcomes Post Myocardial Infarction.
- Author
-
Awolope, Anna, Datta, Esha, Ballal, Aditya, Izu, Leighton T, and López, Javier E.
- Subjects
ELECTRONIC health records ,MYOCARDIAL infarction ,DATA recorders & recording ,DATA analysis ,TREATMENT effectiveness - Published
- 2023
- Full Text
- View/download PDF
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