Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach
<i>Escherichia albertii</i> is an emerging, enteric pathogen of significance. It was first isolated in 2003 from a pediatric diarrheal sample from Bangladesh. In this study, a comprehensive in silico strategy was followed to first list out antibiotic-resistant genes from core, accessory...
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MDPI AG
2023-02-01
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| author | Khurshid Jalal Kanwal Khan Ajmal Hayat Sulaiman Mohammed Alnasser Alotaibi Meshal Zarrin Basharat |
| author_facet | Khurshid Jalal Kanwal Khan Ajmal Hayat Sulaiman Mohammed Alnasser Alotaibi Meshal Zarrin Basharat |
| author_sort | Khurshid Jalal |
| collection | DOAJ |
| description | <i>Escherichia albertii</i> is an emerging, enteric pathogen of significance. It was first isolated in 2003 from a pediatric diarrheal sample from Bangladesh. In this study, a comprehensive in silico strategy was followed to first list out antibiotic-resistant genes from core, accessory and unique genome fractions of 95 available genomes of <i>E. albertii</i>. Then, 56 drug targets were identified from the core essential genome. Finally, ZipA, an essential cell division protein that stabilizes the FtsZ protofilaments by cross-linking them and serves as a cytoplasmic membrane anchor for the Z ring, was selected for further downstream processing. It was computationally modeled using a threading approach, followed by virtual screening of two phytochemical libraries, Ayurvedic (n = 2103 compounds) and Traditional Chinese Medicine (n = 36,043 compounds). ADMET profiling, followed by PBPK modeling in the central body compartment, in a population of 250 non-diseased, 250 cirrhotic and 250 renally impaired people was attempted. ZINC85624912 from Chinese medicinal library showed the highest bioavailability and plasma retention. This is the first attempt to simulate the fate of natural products in the body through PBPK. Dynamics simulation of 20 ns for the top three compounds from both libraries was also performed to validate the stability of the compounds. The obtained information from the current study could aid wet-lab scientists to work on the scaffold of screened drug-like compounds from natural resources and could be useful in our quest for therapy against antibiotic-resistant <i>E. albertii</i>. |
| first_indexed | 2024-03-11T08:32:39Z |
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| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T08:32:39Z |
| publishDate | 2023-02-01 |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-99dbc93d79a943f0ab7174689ca353f22023-11-16T21:42:40ZengMDPI AGLife2075-17292023-02-0113254110.3390/life13020541Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico ApproachKhurshid Jalal0Kanwal Khan1Ajmal Hayat2Sulaiman Mohammed Alnasser3Alotaibi Meshal4Zarrin Basharat5H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDepartment of Pharmacy, Abdul Wali Khan University, Mardan 23200, PakistanDepartment of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Buraydah 52571, Saudi ArabiaDepartment of Pharmacy Practice, College of Pharmacy, University of Hafr Albatin, Hafar Al Batin 39524, Saudi ArabiaJamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan<i>Escherichia albertii</i> is an emerging, enteric pathogen of significance. It was first isolated in 2003 from a pediatric diarrheal sample from Bangladesh. In this study, a comprehensive in silico strategy was followed to first list out antibiotic-resistant genes from core, accessory and unique genome fractions of 95 available genomes of <i>E. albertii</i>. Then, 56 drug targets were identified from the core essential genome. Finally, ZipA, an essential cell division protein that stabilizes the FtsZ protofilaments by cross-linking them and serves as a cytoplasmic membrane anchor for the Z ring, was selected for further downstream processing. It was computationally modeled using a threading approach, followed by virtual screening of two phytochemical libraries, Ayurvedic (n = 2103 compounds) and Traditional Chinese Medicine (n = 36,043 compounds). ADMET profiling, followed by PBPK modeling in the central body compartment, in a population of 250 non-diseased, 250 cirrhotic and 250 renally impaired people was attempted. ZINC85624912 from Chinese medicinal library showed the highest bioavailability and plasma retention. This is the first attempt to simulate the fate of natural products in the body through PBPK. Dynamics simulation of 20 ns for the top three compounds from both libraries was also performed to validate the stability of the compounds. The obtained information from the current study could aid wet-lab scientists to work on the scaffold of screened drug-like compounds from natural resources and could be useful in our quest for therapy against antibiotic-resistant <i>E. albertii</i>.https://www.mdpi.com/2075-1729/13/2/541emerging pathogens<i>Escherichia albertii</i>phytochemicalsZipAtraditional Chinese medicineAyurvedic medicine |
| spellingShingle | Khurshid Jalal Kanwal Khan Ajmal Hayat Sulaiman Mohammed Alnasser Alotaibi Meshal Zarrin Basharat Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach Life emerging pathogens <i>Escherichia albertii</i> phytochemicals ZipA traditional Chinese medicine Ayurvedic medicine |
| title | Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach |
| title_full | Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach |
| title_fullStr | Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach |
| title_full_unstemmed | Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach |
| title_short | Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach |
| title_sort | pan genomics of i escherichia albertii i for antibiotic resistance profiling in different genome fractions and natural product mediated intervention in silico approach |
| topic | emerging pathogens <i>Escherichia albertii</i> phytochemicals ZipA traditional Chinese medicine Ayurvedic medicine |
| url | https://www.mdpi.com/2075-1729/13/2/541 |
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