Lipoteichoic acid deficiency permits normal growth but impairs virulence of Streptococcus pneumoniae

Nathalie Heß, Franziska Waldow, Thomas P. Kohler, Manfred Rohde, Bernd Kreikemeyer, Alejandro Gómez-Mejia, Torsten Hain, Dominik Schwudke, Waldemar Vollmer, Sven Hammerschmidt () and Nicolas Gisch ()
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Nathalie Heß: Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald
Franziska Waldow: Priority Area Infections, Research Center Borstel, Leibniz-Center for Medicine and Biosciences
Thomas P. Kohler: Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald
Manfred Rohde: HZI - Helmholtz Centre for Infection Research
Bernd Kreikemeyer: Institute of Medical Microbiology, Virology and Hygiene, Rostock University
Alejandro Gómez-Mejia: Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald
Torsten Hain: Justus-Liebig University of Giessen
Dominik Schwudke: Priority Area Infections, Research Center Borstel, Leibniz-Center for Medicine and Biosciences
Waldemar Vollmer: Institute for Cell and Molecular Biosciences, Newcastle University
Sven Hammerschmidt: Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald
Nicolas Gisch: Priority Area Infections, Research Center Borstel, Leibniz-Center for Medicine and Biosciences

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Teichoic acid (TA), a crucial cell wall constituent of the pathobiont Streptococcus pneumoniae, is bound to peptidoglycan (wall teichoic acid, WTA) or to membrane glycolipids (lipoteichoic acid, LTA). Both TA polymers share a common precursor synthesis pathway, but differ in the final transfer of the TA chain to either peptidoglycan or a glycolipid. Here, we show that LTA exhibits a different linkage conformation compared to WTA, and identify TacL (previously known as RafX) as a putative lipoteichoic acid ligase required for LTA assembly. Pneumococcal mutants deficient in TacL lack LTA and show attenuated virulence in mouse models of acute pneumonia and systemic infections, although they grow normally in culture. Hence, LTA is important for S. pneumoniae to establish systemic infections, and TacL represents a potential target for antimicrobial drug development.

Date: 2017
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DOI: 10.1038/s41467-017-01720-z

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