Fine-tuning of choline metabolism is important for pneumococcal colonization

Johnston, Calum; Hauser, Christoph; Hermans, Peter W.M.; Martin, Bernard; Polard, Patrice; Bootsma, Hester J.; Claverys, Jean-Pierre (2016). Fine-tuning of choline metabolism is important for pneumococcal colonization. Molecular microbiology, 100(6), pp. 972-988. Blackwell Science 10.1111/mmi.13360

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Hauser, Christoph

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0950-382X

Publisher:

Blackwell Science

Language:

English

Submitter:

Christoph Victor Hauser

Date Deposited:

07 Feb 2017 10:40

Last Modified:

16 Feb 2017 14:22

Publisher DOI:

10.1111/mmi.13360

PubMed ID:

26919406

Additional Information:

Johnston and Hauser contributed equally to this publication (joined first authors)

BORIS DOI:

10.7892/boris.83527

URI:

https://boris.unibe.ch/id/eprint/83527

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