title: Fine-tuning of choline metabolism is important for pneumococcal colonization.
abstract: 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 Plic1P1 and Plic1P2 controlling lic1 and Plic2 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. Plic1P1 , 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 Plic1P1 , 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 Plic1P1 in response to choline was important for pneumococcal colonization. We suggest that derepression of Plic1P1 upon choline depletion maximizing choline internalization constitutes an adaptive response mechanism allowing pneumococci to optimize growth and survival in environments where choline is scarce.
authors.affiliation: Centre National de la Recherche Scientifique, LMGM-UMR5100, F-31000, Toulouse, France.|Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, F-31000, Toulouse, France.
authors.forename: Calum
authors.initials: C
authors.lastname: Johnston
authors.affiliation: Centre National de la Recherche Scientifique, LMGM-UMR5100, F-31000, Toulouse, France.|Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, F-31000, Toulouse, France.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hauser
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Hermans
authors.affiliation: Centre National de la Recherche Scientifique, LMGM-UMR5100, F-31000, Toulouse, France.|Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, F-31000, Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Martin
authors.affiliation: Centre National de la Recherche Scientifique, LMGM-UMR5100, F-31000, Toulouse, France.|Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, F-31000, Toulouse, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Polard
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: Hester J
authors.initials: HJ
authors.lastname: Bootsma
authors.affiliation: Centre National de la Recherche Scientifique, LMGM-UMR5100, F-31000, Toulouse, France.|Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, F-31000, Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Claverys
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002794:Choline / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051379:Mice; D009876:Operon; D011008:Pneumococcal Infections / Q000382:microbiology; D011401:Promoter Regions, Genetic; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D013682:Teichoic Acids / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D013682:Teichoic Acids; D002794:Choline