Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection
| Autor: | Steffen Bernecker, Rolf Jansen, Rolf Müller, Christine M. Gillen, Torsten G. Loof, Katharina Rox, Gursharan S. Chhatwal, Mark J. Walker |
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| Přispěvatelé: | Helmholtz-Institut für pharmazeutische Forschung Saarland,Universitätscampus E8.1, 66123 Saarbrücken, Germany. |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Streptococcus pyogenes Plasmin Streptokinase Linoleic acid 030106 microbiology lcsh:Medicine Mice Transgenic Biology medicine.disease_cause Article Caproic Acid Cell Line Microbiology Fatty Acids Monounsaturated Linoleic Acid Sepsis Mice 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Streptococcal Infections medicine Animals Humans Palmitoleic acid lcsh:Science Multidisciplinary Streptococcus lcsh:R Plasminogen medicine.disease 030104 developmental biology chemistry lcsh:Q medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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