posted on 2023-10-03, 11:19authored byDG Glanville, O Gazioglu, M Marra, VL Tokars, T Kushnir, M Habtom, NJ Croucher, YM Nebenzahl, A Mondragón, H Yesilkaya, AT Ulijasz
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.
Funding
Research was supported by National Institute of Health grants R011AI35060 awarded to A.T.U and R35-GM118108 to A.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
History
Citation
Glanville DG, Gazioglu O, Marra M, Tokars VL, Kushnir T, Habtom M, et al. (2023) Pneumococcal capsule expression is controlled
through a conserved, distal cis-regulatory element during infection. PLoS Pathog 19(1): e1011035