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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621136
Title:
Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection
Authors:
Rox, Katharina; Jansen, Rolf; Loof, Torsten G.; Gillen, Christine M.; Bernecker, Steffen; Walker, Mark J.; Chhatwal, Gursharan Singh; Müller, Rolf ( 0000-0002-1042-5665 )
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.
Affiliation:
Helmholtz-Institut für pharmazeutische Forschung Saarland,Universitätscampus E8.1, 66123 Saarbrücken, Germany.
Citation:
Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection 2017, 7 (1) Scientific Reports
Journal:
Scientific Reports
Issue Date:
18-Sep-2017
URI:
http://hdl.handle.net/10033/621136
DOI:
10.1038/s41598-017-11276-z
Additional Links:
http://www.nature.com/articles/s41598-017-11276-z
Type:
Article
ISSN:
2045-2322
Appears in Collections:
publications of the scientific administration (GFW); publications of the department of microbial natural substances ([HIPS]MINS)

Full metadata record

DC FieldValue Language
dc.contributor.authorRox, Katharinaen
dc.contributor.authorJansen, Rolfen
dc.contributor.authorLoof, Torsten G.en
dc.contributor.authorGillen, Christine M.en
dc.contributor.authorBernecker, Steffenen
dc.contributor.authorWalker, Mark J.en
dc.contributor.authorChhatwal, Gursharan Singhen
dc.contributor.authorMüller, Rolfen
dc.date.accessioned2017-10-12T09:13:35Z-
dc.date.available2017-10-12T09:13:35Z-
dc.date.issued2017-09-18-
dc.identifier.citationLinoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection 2017, 7 (1) Scientific Reportsen
dc.identifier.issn2045-2322-
dc.identifier.doi10.1038/s41598-017-11276-z-
dc.identifier.urihttp://hdl.handle.net/10033/621136-
dc.description.abstractIn 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.en
dc.relation.urlhttp://www.nature.com/articles/s41598-017-11276-zen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleLinoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection-
dc.typeArticleen
dc.contributor.departmentHelmholtz-Institut für pharmazeutische Forschung Saarland,Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalScientific Reportsen
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