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Promiscuous signaling by a regulatory system unique to the pandemic PMEN1 pneumococcal lineage

Anagha Kadam1, Rory A Eutsey1, Jason Rosch2

  • 1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.

Plos Pathogens
|May 26, 2017
PubMed

Insights

The TprA2/PhrA2 system in Streptococcus pneumoniae regulates lung disease by controlling lcpA gene expression. This system promotes commensalism and influences inter-strain gene regulation.

Area of Science:

  • Microbiology
  • Genomics
  • Bacterial Pathogenesis

Background:

  • Streptococcus pneumoniae causes significant global mortality and morbidity, particularly in vulnerable populations.
  • High genetic variability in S. pneumoniae arises from gene gain/loss, impacting virulence and ecological fitness.
  • The PMEN1 lineage is a prevalent, multidrug-resistant strain with unique genetic adaptations.

Purpose of the Study:

  • To investigate the function and impact of the TprA2/PhrA2 regulator-peptide system in the S. pneumoniae PMEN1 lineage.
  • To determine the role of TprA2/PhrA2 in bacterial colonization, disease progression, and inter-strain interactions.
  • To understand how horizontal gene transfer contributes to the evolution of pneumococcal virulence and regulation.

Main Methods:

  • Comparative genomics to identify the presence and distribution of the TprA2/PhrA2 system in PMEN1 strains.
  • Molecular biology techniques to study the regulatory interactions between TprA2, PhrA2, and lcpA.
  • In vivo studies using a mouse model of pneumococcal intranasal inoculation to assess colonization and lung disease.

Main Results:

  • The TprA2/PhrA2 system was acquired by a PMEN1 ancestor and is widespread in this lineage.
  • TprA2 acts as a negative regulator of the PMEN1-specific lanthionine-containing peptide gene (lcpA), with activity modulated by PhrA2.
  • In vivo, TprA2 reduced lung disease severity by controlling lcpA expression, without affecting nasopharyngeal colonization.
  • The PhrA2 peptide can activate a second regulator-peptide system (TprA/PhrA), influencing gene expression in multiple pneumococcal lineages.

Conclusions:

  • The TprA2/PhrA2 system provides PMEN1 isolates with a mechanism to balance commensalism and dissemination, thereby controlling lung disease.
  • Acquisition of this system allows for regulation of inter-strain interactions and adaptation to host environments.
  • This study highlights the role of horizontal gene transfer in shaping pneumococcal virulence and regulatory networks.

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