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.

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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