Notice bibliographique
Résumé
Mycobacterium tuberculosis and Mycobacterium avium subsp. paratuberculosis (MAP) are important human and animal pathogens, respectively. Previous studies indicate that these two host-adapted pathogenic species have emerged from closely-related environmental strains that rarely cause disease. Through comparative genomic studies, our research group has observed a common, biphasic pattern of evolution that independently gave rise to these pathogenic species, characterized by gene acquisition via horizontal gene transfer (HGT), followed by gene deletion. As HGT is an important mechanism for bacteria to integrate novel genetic material into their genomes, yet was considered until recently to not occur in mycobacteria, we are particularly interested in its evolutionary significance in this genus. Our hypothesis is that the acquisition of virulence factors via HGT contributed to the emergence of these two professional pathogens. In this thesis, I aim to identify and characterize genomic differences between these two host-adapted mycobacterial pathogens and their genetically-closest environmental counterparts, using both a genome-wide discovery approach and targeted investigation of a candidate locus identified through genomic studies. In the example of MAP, use of transposon (Tn) mutagenesis mediated genome-wide screen showed MAP-specific genes are under-represented in genes required for growth in vitro, but over-represented for in vivo survival. One of the MAP-specific genes, MAP3776c, is required for full fitness in vivo. MAP3776c belongs to a 5-gene MAP-specific genomic island, LSPP15 (MAP3776-2c) that we experimentally showed codes for an iron acquisition system. As MAP has long been recognized as a siderophore auxotroph, our genomic analysis reveals that the acquisition of LSPP15 provides MAP with an alternative machinery for MAP to acquire metals such as iron in vivo. Applying this paradigm to the study of M. tuberculosis, we showed that many currently-accepted virulence factors of this organism are shared with M. kansasii, an environmental mycobacterium incapable of human-to-human transmission. This observation prompted us to pursue functional characterization of a M. tuberculosis-specific gene pair, akin to our MAP LSPP15 study. The introduction of the M. tuberculosis genes, Rv3377c-78c, into M. kansasii, resulted in the production in M. kansasii of tuberculosinol-adenosine, providing proof-of-principle that one can model in the laboratory discrete steps in the emergence of M. tuberculosis from an environmental ancestor. Overall these findings provide independent lines of evidence that HGT events have contributed to the parallel emergence of these important pathogenic mycobacteria. This work is expected to stimulate further investigations that characterize the unique virulence attributes that define pathogenic mycobacteria of medical and veterinary relevance.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».