Highly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620517
Title:
Highly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae.
Authors:
Kuipers, Kirsten; Gallay, Clement; Martínek, Václav; Rohde, Manfred ( 0000-0003-0522-3580 ) ; Martínková, Markéta; van der Beek, Samantha L; Jong, Wouter S P; Venselaar, Hanka; Zomer, Aldert; Bootsma, Hester; Veening, Jan-Willem; de Jonge, Marien I
Abstract:
Proteins belonging to the DHH family, a member of the phosphoesterase superfamily, are produced by most bacterial species. While some of these proteins are well studied in Bacillus subtilis and Escherichia coli, their functions in Streptococcus pneumoniae remain unclear. Recently, the highly conserved DHH subfamily 1 protein PapP (SP1298) has been reported to play an important role in virulence. Here, we provide a plausible explanation for the attenuated virulence of the papP mutant. Recombinant PapP specifically hydrolyzed nucleotides 3'-phosphoadenosine-5'-phosphate (pAp) and 5'-phosphoadenylyl-(3'->5')-adenosine (pApA). Deletion of papP, potentially leading to pAp/pApA accumulation, resulted in morphological defects and mis-localization of several cell division proteins. Incubation with both polar solvent and detergent led to robust killing of the papP mutant, indicating that membrane integrity is strongly affected. This is in line with previous studies showing that pAp inhibits the ACP synthase, an essential enzyme involved in lipid precursor production. Remarkably, partial inactivation of the lipid biosynthesis pathway, by inhibition of FabF or depletion of FabH, phenocopied the papP mutant. We conclude that pAp and pApA phosphatase activity of PapP is required for maintenance of membrane lipid homeostasis providing an explanation how inactivation of this protein may attenuate pneumococcal virulence.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig.
Citation:
Highly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae. 2016, 101 (1):12-26 Mol. Microbiol.
Journal:
Molecular microbiology
Issue Date:
Jul-2016
URI:
http://hdl.handle.net/10033/620517
DOI:
10.1111/mmi.13312
PubMed ID:
26691161
Type:
Article
Language:
en
ISSN:
1365-2958
Appears in Collections:
publications of the central unit for microscopy (ZEIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorKuipers, Kirstenen
dc.contributor.authorGallay, Clementen
dc.contributor.authorMartínek, Václaven
dc.contributor.authorRohde, Manfreden
dc.contributor.authorMartínková, Markétaen
dc.contributor.authorvan der Beek, Samantha Len
dc.contributor.authorJong, Wouter S Pen
dc.contributor.authorVenselaar, Hankaen
dc.contributor.authorZomer, Alderten
dc.contributor.authorBootsma, Hesteren
dc.contributor.authorVeening, Jan-Willemen
dc.contributor.authorde Jonge, Marien Ien
dc.date.accessioned2016-09-19T10:42:13Z-
dc.date.available2016-09-19T10:42:13Z-
dc.date.issued2016-07-
dc.identifier.citationHighly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae. 2016, 101 (1):12-26 Mol. Microbiol.en
dc.identifier.issn1365-2958-
dc.identifier.pmid26691161-
dc.identifier.doi10.1111/mmi.13312-
dc.identifier.urihttp://hdl.handle.net/10033/620517-
dc.description.abstractProteins belonging to the DHH family, a member of the phosphoesterase superfamily, are produced by most bacterial species. While some of these proteins are well studied in Bacillus subtilis and Escherichia coli, their functions in Streptococcus pneumoniae remain unclear. Recently, the highly conserved DHH subfamily 1 protein PapP (SP1298) has been reported to play an important role in virulence. Here, we provide a plausible explanation for the attenuated virulence of the papP mutant. Recombinant PapP specifically hydrolyzed nucleotides 3'-phosphoadenosine-5'-phosphate (pAp) and 5'-phosphoadenylyl-(3'->5')-adenosine (pApA). Deletion of papP, potentially leading to pAp/pApA accumulation, resulted in morphological defects and mis-localization of several cell division proteins. Incubation with both polar solvent and detergent led to robust killing of the papP mutant, indicating that membrane integrity is strongly affected. This is in line with previous studies showing that pAp inhibits the ACP synthase, an essential enzyme involved in lipid precursor production. Remarkably, partial inactivation of the lipid biosynthesis pathway, by inhibition of FabF or depletion of FabH, phenocopied the papP mutant. We conclude that pAp and pApA phosphatase activity of PapP is required for maintenance of membrane lipid homeostasis providing an explanation how inactivation of this protein may attenuate pneumococcal virulence.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleHighly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig.en
dc.identifier.journalMolecular microbiologyen
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