| Titre : | SHOTGUN COMPARATIVE PROTEOMICS FOR IDENTIFICATION OF DRUG RESISTANCE SIGNATURES IN MYCOBACTERIUM TUBERCULOSIS ISOLATES | | Type de document : | thèse | | Auteurs : | ELHAOU FATIMA EZZAHRAA, Auteur | | Année de publication : | 2023 | | Langues : | Anglais (eng) | | Mots-clés : | Tuberculosis Mycobacterium tuberculosis Comparative-proteomics Mass spectrometry Drug resistance Tuberculose Mycobacterium tuberculosis Protéomique-comparative Spectrométrie de masse Résistance aux antituberculeux السل المتفطرة السلية البروتينات المقارنة مطياف الكتلة مقاومة الأدوية | | Résumé : | Tuberculosis (TB) is a persistent global health issue, especially due to the emergence of drug-resistant strains. Although TB rates have decreased worldwide, it remains a significant problem in certain regions like Morocco. In this study, we employed a Label-Free shotgun comparative proteomic approach to analyse protein expression differences between drugresistant and drug-sensitive Mycobacterium tuberculosis (MTB) isolates. To conduct the proteomic analysis, we used trypsin digestion in a bottom-up proteomic strategy to generate peptide fragments for further analysis. Ultra High-Performance Liquid Chromatography coupled with tandem mass spectrometry (LC-MS/MS) was utilized to separate and analyse these peptide fragments, enabling the identification and quantification of proteins in the drug-resistant and drug-sensitive MTB samples. By comparing the protein expression levels, we identified several proteins that were downregulated or upregulated in the multidrugresistant (MDR) samples compared to the drug-sensitive ones. Additionally, we quantified twenty proteins that were not expressed in the drug-sensitive samples and among these was the protein UPPP known to confer drug resistance to bacteria due its role in cell wall biosynthesis. Functional annotation and protein interaction networks were employed and elucidated the roles of these proteins in virulence and drug resistance mechanisms. Leveraging proteomic approaches to study the differential expression of these proteins holds great significance in exploring effective strategies for controlling drug resistance in Tuberculosis.
| | Numéro (Thèse ou Mémoire) : | MM0202023 | | Président : | OUADGHIRI Mouna | | Directeur : | El ALLALI Achraf | | Juge : | DAOUD Rachid | | Juge : | BENTAYEBI Kaoutar |
SHOTGUN COMPARATIVE PROTEOMICS FOR IDENTIFICATION OF DRUG RESISTANCE SIGNATURES IN MYCOBACTERIUM TUBERCULOSIS ISOLATES [thèse] / ELHAOU FATIMA EZZAHRAA, Auteur . - 2023. Langues : Anglais ( eng) | Mots-clés : | Tuberculosis Mycobacterium tuberculosis Comparative-proteomics Mass spectrometry Drug resistance Tuberculose Mycobacterium tuberculosis Protéomique-comparative Spectrométrie de masse Résistance aux antituberculeux السل المتفطرة السلية البروتينات المقارنة مطياف الكتلة مقاومة الأدوية | | Résumé : | Tuberculosis (TB) is a persistent global health issue, especially due to the emergence of drug-resistant strains. Although TB rates have decreased worldwide, it remains a significant problem in certain regions like Morocco. In this study, we employed a Label-Free shotgun comparative proteomic approach to analyse protein expression differences between drugresistant and drug-sensitive Mycobacterium tuberculosis (MTB) isolates. To conduct the proteomic analysis, we used trypsin digestion in a bottom-up proteomic strategy to generate peptide fragments for further analysis. Ultra High-Performance Liquid Chromatography coupled with tandem mass spectrometry (LC-MS/MS) was utilized to separate and analyse these peptide fragments, enabling the identification and quantification of proteins in the drug-resistant and drug-sensitive MTB samples. By comparing the protein expression levels, we identified several proteins that were downregulated or upregulated in the multidrugresistant (MDR) samples compared to the drug-sensitive ones. Additionally, we quantified twenty proteins that were not expressed in the drug-sensitive samples and among these was the protein UPPP known to confer drug resistance to bacteria due its role in cell wall biosynthesis. Functional annotation and protein interaction networks were employed and elucidated the roles of these proteins in virulence and drug resistance mechanisms. Leveraging proteomic approaches to study the differential expression of these proteins holds great significance in exploring effective strategies for controlling drug resistance in Tuberculosis.
| | Numéro (Thèse ou Mémoire) : | MM0202023 | | Président : | OUADGHIRI Mouna | | Directeur : | El ALLALI Achraf | | Juge : | DAOUD Rachid | | Juge : | BENTAYEBI Kaoutar |
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