Mol Microbiol. 2015 Dec 21. doi: 10.1111/mmi.13312. [Epub ahead of print]

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

Kuipers K1, Gallay C2, Martínek V3, Rohde M4, Martínková M3, van der Beek SL1, Jong WS5, Venselaar H6, Zomer A7,Bootsma H8, Veening JW2, de Jonge MI1.

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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. This article is protected by copyright. All rights reserved.

© 2015 John Wiley & Sons Ltd.


FtsZ; PapP; Streptococcus pneumoniae; cell division; fatty acid synthesis; membrane integrity; nucleotide phosphatase; pAp and pApA

PMID: 26691161 [PubMed - as supplied by publisher]