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Updated: Mar 17, 2026

Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092
Published on: October 2, 2017
ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae
Eleanor Fleming1, Andrew Camilli2
1Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Howard Hughes Medical Institute, and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA.
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.
Insights
Streptococcus pneumoniae uses the ManLMN transporter to utilize various sugars and regulate gene expression. This system is crucial for the bacteria
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Pathogenesis
Background:
- Streptococcus pneumoniae colonizes the human nasopharynx and causes diseases like pneumonia.
- This bacterium utilizes host-derived carbohydrates for energy, demonstrating adaptability in nutrient metabolism.
- Carbon catabolite repression (CCR) is a key regulatory mechanism in bacteria for efficient nutrient utilization.
Purpose of the Study:
- To investigate the role of the conserved PTS ManLMN transporter in Streptococcus pneumoniae.
- To understand how ManLMN contributes to carbohydrate metabolism and gene regulation.
- To elucidate the integration of ManLMN within the bacterium's carbon catabolite repression (CCR) regulatory network.
Main Methods:
- Phenotypic analysis of S. pneumoniae growth on various carbohydrates.
- Genetic analysis, including suppressor selection, to identify regulatory components.
- Transcriptional analysis to assess gene expression changes.
- Characterization of hypothetical small proteins involved in regulation.
Main Results:
- The ManLMN transporter is essential for growth on glucose and other carbohydrates, functioning as a multisubstrate transporter.
- ManLMN is required for inducing downstream metabolic gene expression in response to carbohydrate availability.
- ManLMN plays a unique, constitutive role in S. pneumoniae's CCR strategy.
- Two hypothetical proteins and the virulence regulator SmrC were identified as potential mediators of CCR linked to ManLMN.
Conclusions:
- ManLMN is a versatile carbohydrate transporter critical for S. pneumoniae's metabolic flexibility and virulence.
- The ManLMN transporter is integral to the bacterium's CCR mechanism, influencing the expression of metabolic genes.
- Hypothetical proteins and SmrC are implicated in mediating CCR, highlighting a complex regulatory network.
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