Premium
Fine‐tuning of choline metabolism is important for pneumococcal colonization
Author(s) -
Johnston Calum,
Hauser Christoph,
Hermans Peter W. M.,
Martin Bernard,
Polard Patrice,
Bootsma Hester J.,
Claverys JeanPierre
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13360
Subject(s) - derepression , choline , biology , phosphocholine , operon , repressor , biochemistry , teichoic acid , choline kinase , bacillus subtilis , microbiology and biotechnology , psychological repression , mutant , enzyme , gene expression , bacteria , gene , genetics , phospholipid , peptidoglycan , phosphatidylcholine , membrane
Summary The human pathogen Streptococcus pneumoniae (the pneumococcus) is rare in having a strict requirement for the amino alcohol choline, which decorates pneumococcal teichoic acids. This process relies on the lic locus, containing the lic1 and lic2 operons. These operons produce eight proteins that import and metabolize choline, generate teichoic acid precursors and decorate these with choline. Three promoters control expression of lic operons, with P lic1P1 and P lic1P2 controlling lic1 and P lic2 controlling lic2 . To investigate the importance of lic regulation for pneumococci, we assayed the activity of transcriptional fusions of the three lic promoters to the luciferase reporter gene. P lic1P1 , whose activity depends on the response regulator CiaR, responded to fluctuations in extracellular choline, with activity increasing greatly upon choline depletion. We uncovered a complex regulatory mechanism controlling P lic1P1 , involving activity driven by CiaR, repression by putative repressor LicR in the presence of choline, and derepression upon choline depletion mediated by LicC, a choline metabolism enzyme. Finally, the ability to regulate P lic1P1 in response to choline was important for pneumococcal colonization. We suggest that derepression of P lic1P1 upon choline depletion maximizing choline internalization constitutes an adaptive response mechanism allowing pneumococci to optimize growth and survival in environments where choline is scarce.