Pneumococcal capsule expression is controlled through a conserved, distal cisregulatory element during infection

David G. Glanville, Ozcan Gazioglu, Michela Marra, Valerie L. Tokars, Tatyana Kushnir, Medhanie Habtom, Nicholas J. Croucher, Yaffa Mizrachi Nebenzahl, Alfonso Mondragón, Hasan Yesilkaya, Andrew T. Ulijasz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial pneumonia in the US and worldwide. Studies have shown that the differing chemical make-up between serotypes of its most important virulence factor, the capsule, can dictate disease severity. Here we demonstrate that control of capsule synthesis is also critical for infection and facilitated by two broadly conserved transcription factors, SpxR and CpsR, through a distal cis-regulatory element we name the 37-CE. Strikingly, changing only three nucleotides within this sequence is sufficient to render pneumococcus avirulent. Using in vivo and in vitro approaches, we present a model where SpxR interacts as a unique trimeric quaternary structure with the 37-CE to enable capsule repression in the airways. Considering its dramatic effect on infection, variation of the 37-CE between serotypes suggests this molecular switch could be a critical contributing factor to this pathogen’s serotype-specific disease outcomes.

Original languageEnglish
Article numbere1011035
JournalPLoS Pathogens
Volume19
Issue number1
DOIs
StatePublished - 1 Jan 2023

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Fingerprint

Dive into the research topics of 'Pneumococcal capsule expression is controlled through a conserved, distal cisregulatory element during infection'. Together they form a unique fingerprint.

Cite this