Synergetic Antimicrobial Activity and Mechanism of Clotrimazole-Linked CO-Releasing Molecules
Sofia S. Mendes, Joana Marques, Edit Mesterházy, Jan Straetener, Melina Arts, Teresa Pissarro, Jorgina Reginold, Anne Berscheid, Jan Bornikoel, Robert Maria Kluj, Christoph Mayer, Filipp Oesterhelt, Sofia Friães, Beatriz Royo, Tanja Schneider, Heike Brötz‐Oesterhelt, Carlos C. Romão, Lı́gia M. Saraiva
Abstract
causes a general impact on the membrane topology, has inhibitory effects on peptidoglycan biosynthesis, and affects energy functions. The mechanism of action of this kind of CORM conjugates involves a sequence of events initiated by membrane insertion, followed by membrane disorganization, inhibition of peptidoglycan synthesis, CO release, and break down of the membrane potential. These results suggest that conjugation of CORMs to known antibiotics may produce useful structures with synergistic effects that increase the conjugate's activity relative to that of the antibiotic alone.