Heparin increases the antibiotic efficacy of colistin

Frontiers in Analytical Science

Analytical Science

Jan Horlebein¹  Daniel Lauster²  Robyn Diehn²  Emeline Hanozin³  Lukasz Polewski³  Kevin Pagel³  Gergo Peter Szekeres³  Andreas Zappe³ 

[1] Department of Molecular Physics, Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin, Germany;Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany;Biopharmaceuticals, Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany;Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany;Department of Molecular Physics, Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin, Germany;

关键词: glycosaminoglycans;    mass spectrometry;    heparin;    colistin;    antibiotic activity;    ion mobility spectrometry;   

DOI  :  10.3389/frans.2023.1154391

 received in 2023-01-30, accepted in 2023-05-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

The increasing antibiotic resistance in bacteria is an alarming phenomenon all around the world. Certain strains have developed resistance against multiple antimicrobial molecules, in which cases, the final option is to use a last-resort drug. These drugs, however, are last-resort for a reason: they can pose serious risk on vital organ functions in the patient. To mitigate the risk of severe side-effects and to reduce the rate of bacterial mutation, co-administration with other molecules that increase their efficacy seems to be the only suitable option. This leads to a reduced dose while maintaining the same level of antibiotic activity within the body. In this study, the effect of heparin derivatives on the antibiotic activity of colistin and their interactions were studied by ion mobility, mass spectrometry, and bacterium growth assays. The results show that during the association of colistin and heparin, they retain their structure while higher-stoichiometry complexes can form. When long-chain heparin is co-administered, multiple colistin molecules can associate with it, which increases the antibiotic activity by ∼40% relative to the sole administration of colistin.

【 授权许可】

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Copyright © 2023 Szekeres, Hanozin, Diehn, Horlebein, Polewski, Zappe, Lauster and Pagel.