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|Title:||Host-glycan metabolism is regulated by a species-conserved two-component system in Streptococcus pneumoniae|
|Citation:||PLoS Pathog, 2020; 16(3):1-27|
|Patrick Rosendahl Andreassen, Claudia Trappetti, Vikrant Minhas, Flemming Damgaard Nielsen, Kevin Pakula, James C. Paton, Mikkel Girke Jørgensen|
|Abstract:||Pathogens of the Streptococcus genus inhabit many different environmental niches during the course of an infection in a human host and the bacteria must adjust their metabolism according to available nutrients. Despite their lack of the citric-acid cycle, some streptococci proliferate in niches devoid of a readily available carbohydrate source. Instead they rely on carbohydrate scavenging for energy acquisition, which are obtained from the host. Here we discover a two-component system (TCS07) of Streptococcus pneumoniae that responds to glycoconjugated structures on proteins present on the host cells. Using next-generation RNA sequencing we find that the uncharacterized TCS07 regulon encodes proteins important for host-glycan processing and transporters of the released glycans, as well as intracellular carbohydrate catabolising enzymes. We find that a functional TCS07 allele is required for growth on the glycoconjugated model protein fetuin. Consistently, we see a TCS07-dependent activation of the glycan degradation pathway. Thus, we pinpoint the molecular constituents responsible for sensing host derived glycans and link this to the induction of the proteins necessary for glycan degradation. Furthermore, we connect the TCS07 regulon to virulence in a mouse model, thereby establishing that host-derived glycan-metabolism is important for infection in vivo. Finally, a comparative phylogenomic analysis of strains from the Streptococcus genus reveal that TCS07 and most of its regulon is specifically conserved in species that utilize host-glycans for growth.|
|Keywords:||Pneumococcus; regulons; DNA-binding proteins; carbohydrates; carbohydrate metabolism; RNA extraction; sialic acids; mouse models|
|Rights:||© 2020 Andreassen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Appears in Collections:||Microbiology and Immunology publications|
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