Carbon source regulates polysaccharide capsule biosynthesis in Streptococcus pneumoniae

Troxler, Lukas J.; Werren, Joel P.; Schaffner, Thierry O.; Mostacci, Nadezda; Vermathen, Peter; Vermathen, Martina; Bruggmann, Rémy; Hathaway, Lucy J.; Furrer, Julien; Hilty, Markus (2019). Carbon source regulates polysaccharide capsule biosynthesis in Streptococcus pneumoniae. Journal of biological chemistry, 294(46), pp. 17224-17238. American Society for Biochemistry and Molecular Biology 10.1074/jbc.RA119.010764

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The exopolysaccharide capsule of Streptococcus pneumoniae is an important virulence factor, but the mechanisms that regulate capsule thickness are not fully understood. Here, we investigated the effects of various exogenously supplied carbohydrates on capsule production and gene expression in several pneumococcal serotypes. Microscopy analyses indicated a near absence of the capsular polysaccharide (CPS) when S. pneumoniae was grown in fructose. Moreover, serotype 7F pneumococci produced much less CPS than strains of other serotypes (6B, 6C, 9V, 15, and 23F) when grown on glucose or sucrose. RNA-Sequencing revealed carbon source–dependent regulation of distinct genes of wildtype strains and capsule-switch mutants of serotypes 6B and 7F, but could not explain the mechanism of capsule thickness regulation. In contrast, 31P NMR of whole-cell extract from capsule-knockout strains (Δcps) clearly revealed the accumulation or absence of capsule precursor metabolites when cells were grown on glucose or fructose, respectively. This finding suggests that fructose uptake mainly results in intracellular fructose-1-phosphate, which is not converted to CPS precursors. In addition, serotype 7F strains accumulated more precursors than did 6B strains, indicating less efficient conversion of precursor metabolites into the CPS in 7F, in line with its thinner capsule. Finally, isotopologue sucrose labeling and NMR analyses revealed that the uptake of the labeled fructose subunit into the capsule is < 10% that of glucose. Our findings on the effects of carbon sources on CPS production in different S. pneumoniae serotypes may contribute to a better understanding of pneumococcal diseases and could inform future therapeutic approaches

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Abt. Magnetresonanz-Spektroskopie und Methodologie, AMSM

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Werren, Joel Pascal; Mostacci, Nadezda; Vermathen, Peter; Vermathen, Martina; Bruggmann, Rémy; Hathaway, Lucy Jane; Furrer, Julien and Hilty, Markus

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Markus Hilty

Date Deposited:

21 Oct 2019 13:54

Last Modified:

19 Nov 2019 01:32

Publisher DOI:

10.1074/jbc.RA119.010764

PubMed ID:

31594867

BORIS DOI:

10.7892/boris.134050

URI:

https://boris.unibe.ch/id/eprint/134050

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