Highly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae. Issue 1 (19th February 2016)

• Record Type: Journal Article
• Authors: Kuipers, Kirsten; Gallay, Clement; Martínek, Václav; Rohde, Manfred; Martínková, Markéta; van der Beek, Samantha L.; Jong, Wouter S. P.; Venselaar, Hanka; Zomer, Aldert; Bootsma, Hester; Veening, Jan‐Willem; de Jonge, Marien I.
• Is Part Of: Molecular microbiology. Volume 101:Issue 1(2016)
• Page Start: 12
• Page End: 26
• Publication Date: 2016-02-19
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13312
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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. Abstract : The nucleotide phosphatase PapP was reported to play an important role in virulence of Streptococcus pneumoniae . PapP is able to hydrolyse pAp and pApA, two compounds produced during lipid biosynthesis and ci‐di‐AMP degradation. Deletion of papP resulted in membrane integrity alteration, morphological defects and mis‐localization of cell division proteins. Furthermore, partial inactivation of lipid biosynthesis pathway phenocopied Δ papP mutant. Taken together, the data support a role for PapP in membrane lipid homeostasis.