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Sci Rep. 2017 Sep 18;7(1):11798. doi: 10.1038/s41598-017-11276-z.

Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection.

Author information

1
Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbrücken, Germany.
2
Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
3
Central facility for Microscopy, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
4
German Centre for Infection Research (DZIF), Partner Site Braunschweig-Hannover, Hannover, Germany.
5
Department of Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
6
Infection Immunology Research Group, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
7
School of Chemistry and Molecular Biosciences and Australian Infectious Disease Research Centre, The University of Queensland, St. Lucia, Queensland, Australia.
8
Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbrücken, Germany. rolf.mueller@helmholtz-hzi.de.
9
German Centre for Infection Research (DZIF), Partner Site Braunschweig-Hannover, Hannover, Germany. rolf.mueller@helmholtz-hzi.de.

Abstract

In contrast to mild infections of Group A Streptococcus (GAS) invasive infections of GAS still pose a serious health hazard: GAS disseminates from sterile sites into the blood stream or deep tissues and causes sepsis or necrotizing fasciitis. In this case antibiotics do not provide an effective cure as the bacteria are capable to hide from them very quickly. Therefore, new remedies are urgently needed. Starting from a myxobacterial natural products screening campaign, we identified two fatty acids isolated from myxobacteria, linoleic and palmitoleic acid, specifically blocking streptokinase-mediated activation of plasminogen and thereby preventing streptococci from hijacking the host's plasminogen/plasmin system. This activity is not inherited by other fatty acids such as oleic acid and is not attributable to the killing of streptococci. Moreover, both fatty acids are superior in their inhibitory properties compared to two clinically used drugs (tranexamic or ε-amino caproic acid) as they show 500-1000 fold lower IC50 values. Using a humanized plasminogen mouse model mimicking the clinical situation of a local GAS infection that becomes systemic, we demonstrate that these fatty acids ameliorate invasive GAS infection significantly. Consequently, linoleic and palmitoleic acid are possible new options to combat GAS invasive diseases.

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