In Silico Analysis of Mutations in Quinolone Resistance Determinant Region for Flouroquinolone Resistance in <em>Salmonella typhi</em>
Salmonella enterica serovar Typhi, is one of the major infection spreading from consuming contaminated food and water. The poor sanitation is one the major cause for successful infection. S. typhi is responsible for causing typhoid fever, which is a growing public health concern in developing countries. This bacterium has acquired antimicrobial resistance to many promising which is a growing health concern for community. This study is aim to elucidate the molecular complexity of flouroquinolone resistance in S. Typhi isolates (n=286). Genomic data was downloaded from NCBI and analysis was done by Resfinder, MLST, and Pointfinder. Genomic analysis unveils a complex resistance profile, featuring antimicrobial resistance genes (ARG) including blaCTXM-15, blaTEM-1D, catA1, dfrA7, qnrS1, sul1, sul2, and tetA(B). The investigation focuses on mutations in DNA gyrA, parC, and qnrS1 genes which plays an important role in quinolone resistance. Mutation analysis reveals mutations such as DNA gyrA_S83F, DNA gyrA_D87N, DNA gyrA_S83Y, DNA gyrB_S464F, parC_S80I, and parE_L416F with the presence of qnrS1 gene produces resistance against quinolones. The Docking studies was conducted by “Autodock vina” and visualize by “Discovery studio” which demonstrate that these mutations leads to ciprofloxacin resistance, indicating reduced binding affinity, and altered solvent accessibility which indicates the structural changes at mutation sites. This study provides crucial insights into the molecular mechanisms driving flouroquinolone resistance in S. typhi, guiding future strategies to combat antibiotic resistance. Further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. typhi..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Preprints.org - (2024) vom: 01. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khan, Noman [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.20944/preprints202401.2178.v1 |
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| PPN (Katalog-ID): |
preprintsorg042366836 |
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| 245 | 1 | 0 | |a In Silico Analysis of Mutations in Quinolone Resistance Determinant Region for Flouroquinolone Resistance in <em>Salmonella typhi</em> |
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| 520 | |a Salmonella enterica serovar Typhi, is one of the major infection spreading from consuming contaminated food and water. The poor sanitation is one the major cause for successful infection. S. typhi is responsible for causing typhoid fever, which is a growing public health concern in developing countries. This bacterium has acquired antimicrobial resistance to many promising which is a growing health concern for community. This study is aim to elucidate the molecular complexity of flouroquinolone resistance in S. Typhi isolates (n=286). Genomic data was downloaded from NCBI and analysis was done by Resfinder, MLST, and Pointfinder. Genomic analysis unveils a complex resistance profile, featuring antimicrobial resistance genes (ARG) including blaCTXM-15, blaTEM-1D, catA1, dfrA7, qnrS1, sul1, sul2, and tetA(B). The investigation focuses on mutations in DNA gyrA, parC, and qnrS1 genes which plays an important role in quinolone resistance. Mutation analysis reveals mutations such as DNA gyrA_S83F, DNA gyrA_D87N, DNA gyrA_S83Y, DNA gyrB_S464F, parC_S80I, and parE_L416F with the presence of qnrS1 gene produces resistance against quinolones. The Docking studies was conducted by “Autodock vina” and visualize by “Discovery studio” which demonstrate that these mutations leads to ciprofloxacin resistance, indicating reduced binding affinity, and altered solvent accessibility which indicates the structural changes at mutation sites. This study provides crucial insights into the molecular mechanisms driving flouroquinolone resistance in S. typhi, guiding future strategies to combat antibiotic resistance. Further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. typhi. | ||
| 700 | 1 | |a Muneer, Hasan |4 aut | |
| 700 | 1 | |a Ilyas, Muhammad Waqar |4 aut | |
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