Antimicrobial Peptide – Metal Interactions – Relationship between Coordination Chemistry, Structure, Thermodynamics and Mode of Action

Increasing bacterial and fungal drug resistance makes novel, effective antimicrobial treatments actively sought. Because of the general lack of resistance towards AMPs, they are being relied on as a novel class of therapeutics aimed to conquer drug-resistant bacteria and fungi [1]. Biologically indispensable metal ions have a dual effect on the activity of antimicrobial peptides: (i) AMPs bind them, so that microbes cannot get enough metals essential for their life and virulence (withdrawal of metal ions, nutritional immunity) or (ii) AMPs need the given metal ion as a booster of their antimicrobial activity (metal ions affect the AMP charge and/or structure) [2]. The presence of Zn(II) and Cu(II) significantly enhances the antimicrobial activity of calcitermin, an antimicrobial peptide from the fluid of the human airways (a C-terminal cleavage fragment of calgranulin C), SAAPs – anionic peptides from sheep and clavanins – His-rich, cationic peptides from tunicates. MIC breakpoints of several of these complexes are much lower than the ones for commonly used antibiotics and antifungal agents. We discuss the details of the coordination mode, structure and stability of the studied complexes, in order to understand the relationship between their bioinorganic chemistry and mode of action. Financial support by the National Science Centre (UMO-2017/26/A/ST5/00364, SONATA BIS grant to MRZ) is gratefully acknowledged. References [1] J. M. Ageitos, A. Sanchez-Perez, P. Calo-Mata, T. G. Villa, Biochem. Pharmacol., 2017, 133, 117-138. [2] D. Łoboda, H. Kozłowski, M. Rowińska-Żyrek, New J. Chem., 2018, 42, 7560-7568.