From ultrastructural morphology to a potential mechanism of action – The Atomic Force Microscope as innovative tool to evaluate anti-infective natural products

In the course of globally emerging antimicrobial resistances, the identification and characterization of natural products as leads for the innovative drug design against infectious pathogens is of specific importance. To mediate the development of a promising lead from natural origin into a therapeutic agent, detailed knowledge on the mechanism of action (MOA) of a bioactive compound is typically needed but often tedious to acquire. Although analytical techniques like the common “omics”-approaches have simplified the elucidation of a natural product´s (NP) MOA, the conclusive interpretation of the resulting large datasets is still a complex process. In order to offer an alternative approach to the identification and evaluation of a potential MOA or even molecular target of a NP, novel techniques for the focused nanoscopic analysis of biological specimens before and after treatment with anti-infective leads from natural origin are presented. Supported by the development of facile and economic preparation protocols, the use of Atomic Force Microscopy (AFM) as innovative tool to study the ultrastructural morphology of clinically important pathogens will be demonstrated. In order to present the relevance of the morphology-based assessment of a NP´s bioactivity, exemplary studies on the elucidation and evaluation of MOAs from a variety of NPs by AFM will additionally be discussed.