| Titre : | MYCOBACTERIUM TUBERCULOSIS AND SARS-COV-2 GENOMIC ANALYSIS: INPUT INTO OUTBREAKS AND SURVEILLANCE INVESTIGATIONS | | Type de document : | thèse | | Auteurs : | Mariem LAAMARTI, Auteur | | Année de publication : | 2021 | | Langues : | Anglais (eng) | | Mots-clés : | Mycobacterium Tuberculosis SARS-Cov-2 Genomic analysis Phylogeny drug resistance phylodynamic sequencing Mycobacterium Tuberculosis SARS-Cov-2 Analyse genomique Phylogenie resistance aux antibiotique , phylodynamique sequencage التحلیل الجینومي النشوء والتطور المقاومة الدینامیكا النباتیة SARS-CoV- المتفطرة السلیة 2 التسلسل | | Résumé : | Comparative microbial genomics is increasingly used for high-resolution epidemiological
investigation of infectious agents' sources, transmission dynamics and antimicrobial
resistance.
In Chapter II, We performed the sequencing and genomic characterization of M.
Tuberculosis strains from Morocco to get insight into their genomic diversity, drug resistance,
population structure and identify potential mutations associated with drug resistance.
We conducted a whole-genome analysis of nine Morrocan M. tuberculosis isolates;
we identi ed 25 known mutations and 14 novel mutations in drug-associated genes and
provided experimental support for them. We found that all resistance and susceptible
strains clustered with LAM9 and Haarlem, respectively, belonging to the Euro-American
clade. The modelling of GyrA/GyrB mutations showed a decrease in the binding anity
with levo
oxacin.
Chapter III addresses the comparative genomic of SARS-CoV-2 from Morocco to
identify genetic variants as a crucial step in evaluating the spread in Morocco. This
study revealed 108 mutations in their genomes. The analysis haplotype network suggests
di erent sources of SARS-CoV-2 infection in Morocco.
In Chapter IV, we collected SARS-CoV-2 genomes isolated from 80 countries.The results
showed genotypes speci c to geographic location. Moreover, evolution over time has
demonstrated a mechanism of mutation co-accumulation, which might a ect the severity
and spread of the SARS-CoV-2 suggesting that a universal vaccine is more likely to be
ecient for all strains.
On the other hand, the selective pressure analysis revealed negatively selected residues
that could be considered therapeutic targets. We have also created an inclusive uni ed
database that lists all of the genetic variants of the SARS-CoV-2 genomes found in this
study. | | Numéro (Thèse ou Mémoire) : | D0112021 | | Président : | Abdallah BADOU | | Directeur : | Azeddine IBRAHIMI ; Samir SIAH | | Juge : | Rachid ELJAOUDI | | Juge : | Laila SBABOU ; Mohammed EL AZAMI EL IDRISSI ; | | Juge : | Lahcen BELYAMANI ; Mouna OUAD |
MYCOBACTERIUM TUBERCULOSIS AND SARS-COV-2 GENOMIC ANALYSIS: INPUT INTO OUTBREAKS AND SURVEILLANCE INVESTIGATIONS [thèse] / Mariem LAAMARTI, Auteur . - 2021. Langues : Anglais ( eng) | Mots-clés : | Mycobacterium Tuberculosis SARS-Cov-2 Genomic analysis Phylogeny drug resistance phylodynamic sequencing Mycobacterium Tuberculosis SARS-Cov-2 Analyse genomique Phylogenie resistance aux antibiotique , phylodynamique sequencage التحلیل الجینومي النشوء والتطور المقاومة الدینامیكا النباتیة SARS-CoV- المتفطرة السلیة 2 التسلسل | | Résumé : | Comparative microbial genomics is increasingly used for high-resolution epidemiological
investigation of infectious agents' sources, transmission dynamics and antimicrobial
resistance.
In Chapter II, We performed the sequencing and genomic characterization of M.
Tuberculosis strains from Morocco to get insight into their genomic diversity, drug resistance,
population structure and identify potential mutations associated with drug resistance.
We conducted a whole-genome analysis of nine Morrocan M. tuberculosis isolates;
we identi ed 25 known mutations and 14 novel mutations in drug-associated genes and
provided experimental support for them. We found that all resistance and susceptible
strains clustered with LAM9 and Haarlem, respectively, belonging to the Euro-American
clade. The modelling of GyrA/GyrB mutations showed a decrease in the binding anity
with levo
oxacin.
Chapter III addresses the comparative genomic of SARS-CoV-2 from Morocco to
identify genetic variants as a crucial step in evaluating the spread in Morocco. This
study revealed 108 mutations in their genomes. The analysis haplotype network suggests
di erent sources of SARS-CoV-2 infection in Morocco.
In Chapter IV, we collected SARS-CoV-2 genomes isolated from 80 countries.The results
showed genotypes speci c to geographic location. Moreover, evolution over time has
demonstrated a mechanism of mutation co-accumulation, which might a ect the severity
and spread of the SARS-CoV-2 suggesting that a universal vaccine is more likely to be
ecient for all strains.
On the other hand, the selective pressure analysis revealed negatively selected residues
that could be considered therapeutic targets. We have also created an inclusive uni ed
database that lists all of the genetic variants of the SARS-CoV-2 genomes found in this
study. | | Numéro (Thèse ou Mémoire) : | D0112021 | | Président : | Abdallah BADOU | | Directeur : | Azeddine IBRAHIMI ; Samir SIAH | | Juge : | Rachid ELJAOUDI | | Juge : | Laila SBABOU ; Mohammed EL AZAMI EL IDRISSI ; | | Juge : | Lahcen BELYAMANI ; Mouna OUAD |
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