The <i>Streptococcus pyogenes</i> mannose phosphotransferase system (Man-PTS) influences antimicrobial activity and niche-specific nasopharyngeal infection
Notice bibliographique
Résumé
ABSTRACT Streptococcus pyogenes is a human-adapted pathogen that causes a variety of infections including pharyngitis and skin infections, and although this bacterium produces many virulence and host colonization factors, how S. pyogenes competes with the host microbiota is not well understood. Here we detected antimicrobial activity produced from S. pyogenes MGAS8232 that was able to prevent the growth of Micrococcus luteus . This activity was produced when cells were grown in 5% CO 2 and in M17 media supplemented with galactose; however, evaluation of the phenotype with the addition of alternative sugars coupled with genome sequencing experiments revealed the antimicrobial phenotype was not related to classical bacteriocins. To further determine genes involved in the production of this activity, a transposon mutant library in S. pyogenes MGAS8232 was generated. The transposon screen identified the mannose phosphotransferase system (Man-PTS), a major sugar transporter in S. pyogenes , as important for the antimicrobial phenotype. Additional loss-of-function transposon mutants linked to the antimicrobial activity were identified to also be involved in alternative sugar utilization and additionally, the Man-PTS was also further identified from a secondary mutation in a bacteriocin operon mutant. Sugar utilization profiles in all the Man-PTS mutants demonstrated that galactose, mannose, and N-acetylglucosamine utilization was impaired in different Man-PTS mutants. In vitro RNA-seq experiments in high and low glucose concentrations further identified the Man-PTS as a glucose transporter; however, there was no transcriptional regulators or virulence factors affected with the loss of the Man-PTS. A clean deletion in the Man-PTS demonstrated defects in a mouse model of nasopharyngeal infection. Overall, the ability of S. pyogenes to utilize alternative sugars presented by glycans seems to play a role in acute infection and interactions with the endogenous microbial population existing in the nasopharynx. IMPORTANCE Streptococcus pyogenes causes a wide range of infections and is responsible for over 500,000 deaths per year due to invasive infections and post-infection sequelae. The most common clinical manifestation of S. pyogenes however are acute infections such as pharyngitis or impetigo. S. pyogenes can adapt to its environment through alternative sugar metabolism and in this study, we identified an antimicrobial phenotype that was not bacteriocin-related but a by-product of alternative sugar metabolism. Evidently, the mannose phosphotransferase system, a well-studied sugar transporter, was involved in production of the antimicrobial, and was also important for S. pyogenes to utilize alternative sugars and establish nasopharyngeal infection, but not skin infection. Overall, this study identified potential strategies used by S. pyogenes for interactions with the endogenous microbiota and further elucidated the importance of sugar metabolism in acute infection.
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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 | 0,000 | 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) | 0,002 | 0,001 |
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 ».