Staphylococcus aureusLpl protein triggers human host cell invasion via activation of Hsp90 receptor

• DOI: 10.1111/cmi.13111
• Publication Date: 2019-09-13T08:08:42Z
• Authors: Paula M. Tribelli; Arif Luqman; Minh‐Thu Nguyen; Johannes Madlung; Sook‐Ha Fan; Boris Macek; Peter Sass; Katharina Bitschar; Birgit Schittek; Dorothee Kretschmer; Friedrich Götz
• Keywords: Keratinocytes; Male; 0301 basic medicine; Staphylococcus aureus; F-ACTIN; Lipoproteins; INVASION; Foreskin; HSP90 RECEPTOR; Actins; Endocytosis; Recombinant Proteins; 3. Good health; 03 medical and health sciences; Bacterial Proteins; https://purl.org/becyt/ford/1.6; Host-Pathogen Interactions; HaCaT Cells; Humans; HSP90 Heat-Shock Proteins; LPL; https://purl.org/becyt/ford/1; STAPHYLOCOCCUS AUREUS; Cells, Cultured

Staphylococcus aureus is a facultative intracellular pathogen. Recently, it has been shown that the protein part of the lipoprotein-like lipoproteins (Lpls), encoded by the lpl cluster comprising of 10 lpls paralogue genes, increases pathogenicity, delays the G2/M phase transition, and also triggers host cell invasion. Here, we show that a recombinant Lpl1 protein without the lipid moiety binds directly to the isoforms of the human heat shock proteins Hsp90α and Hsp90ß. Synthetic peptides covering the Lpl1 sequence caused a twofold to fivefold increase of S. aureus invasion in HaCaT cells. Antibodies against Hsp90 decrease S. aureus invasion in HaCaT cells and in primary human keratinocytes. Additionally, inhibition of ATPase function of Hsp90 or silencing Hsp90α expression by siRNA also decreased the S. aureus invasion in HaCaT cells. Although the Hsp90ß is constitutively expressed, the Hsp90α isoform is heat-inducible and appears to play a major role in Lpl1 interaction. Pre-incubation of HaCaT cells at 39°C increased both the Hsp90α expression and S. aureus invasion. Lpl1-Hsp90 interaction induces F-actin formation, thus, triggering an endocytosis-like internalisation. Here, we uncovered a new host cell invasion principle on the basis of Lpl-Hsp90 interaction.