Dataset Information

ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae.

ABSTRACT: Streptococcus pneumoniae is a common colonizer of the human nasopharynx and a leading cause of bacterial pneumonia and otitis media, among other invasive diseases. During both colonization and invasive disease S. pneumoniae ferments host-derived carbohydrates as its primary means of generating energy. This pathogen is adept at transporting and metabolizing a wide variety of carbohydrates. We found the highly conserved PTS ManLMN contributes to growth on glucose and is also essential for growth on a variety of nonpreferred carbohydrates, suggesting it is a multisubstrate transporter. Exploration of this phenotype revealed ManLMN is required for inducing expression of downstream metabolic genes in response to carbohydrate stimuli. We further demonstrate that ManLMN's role as a constitutively expressed transporter is likely unique and integral to pneumococcus's strategy of carbon catabolite repression (CCR). Using a selection for suppressors, we explored how ManLMN is integrated into the CCR regulatory framework in S. pneumoniae. We identified two hypothetical small proteins and the virulence regulator SmrC as potential mediators of CCR in connection with ManLMN. Characterization of these two hypothetical proteins revealed they influence transcriptional regulation of carbohydrate transporters. We propose a model unifying these observations in which ManLMN is a versatile surveyor of available carbohydrates in S. pneumoniae.

SUBMITTER: Fleming E

PROVIDER: S-EPMC5116393 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae.

Fleming Eleanor E Camilli Andrew A

Molecular microbiology 20160818 3

Streptococcus pneumoniae is a common colonizer of the human nasopharynx and a leading cause of bacterial pneumonia and otitis media, among other invasive diseases. During both colonization and invasive disease S. pneumoniae ferments host-derived carbohydrates as its primary means of generating energy. This pathogen is adept at transporting and metabolizing a wide variety of carbohydrates. We found the highly conserved PTS ManLMN contributes to growth on glucose and is also essential for growth o ...[more]

PMID: 27472033

Similar Datasets

Project description:In gram-positive bacteria, the transcriptional regulator CcpA is at the core of catabolite control mechanisms. In the human pathogen Streptococcus pneumoniae, links between CcpA and virulence have been established, but its role as a master regulator in different nutritional environments remains to be elucidated. Thus, we performed whole-transcriptome and metabolic analyses of S. pneumoniae D39 and its isogenic ccpA mutant during growth on glucose or galactose, rapidly and slowly metabolized carbohydrates presumably encountered by the bacterium in different host niches. CcpA affected the expression of up to 19% of the genome covering multiple cellular processes, including virulence, regulatory networks and central metabolism. Its prevalent function as a repressor was observed on glucose, but unexpectedly also on galactose. Carbohydrate-dependent CcpA regulation was also observed, as for the tagatose 6-phosphate pathway genes, which were activated by galactose and repressed by glucose. Metabolite analyses revealed that two pathways for galactose catabolism are functionally active, despite repression of the Leloir genes by CcpA. Surprisingly, galactose-induced mixed-acid fermentation apparently required CcpA, since genes involved in this type of metabolism were mostly under CcpA-repression. These findings indicate that the role of CcpA extends beyond transcriptional regulation, which seemingly is overlaid by other regulatory mechanisms. In agreement, CcpA influenced the level of many intracellular metabolites potentially involved in metabolic regulation. Our data strengthen the view that a true understanding of cell physiology demands thorough analyses at different cellular levels. Moreover, integration of transcriptional and metabolic data uncovered a link between CcpA and the association of surface molecules (e.g. capsule) to the cell wall. Hence, CcpA may play a key role in mediating the interaction of S. pneumoniae with its host. Overall, our results support the hypothesis that S. pneumoniae optimizes basic metabolic processes, likely enhancing in vivo fitness, in a CcpA-mediated manner.

Dataset Information

ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae.

Publications

ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets