Cell biology of microbes and pharmacology of antimicrobial drugs explored by Atomic Force Microscopy

Abstract

Antimicrobial molecules have been used for more than 50 years now and are the basis of modern medicine. No surgery can nowdays be imagined to be performed without antibiotics; dreadful diseases like tuberculosis, leprosis, siphilys, and more broadly all microbial induced diseases, can be cured only through the use of antimicrobial treatments. However, the situation is becoming more and more complex because of the ability of microbes to adapt, develop, acquire, and share mechanisms of resistance to antimicrobial agents. We choose to introduce this review by briefly drawing the panorama of antimicrobial discovery and development, but also of the emergence of microbial resistance. Then we describe how Atomic Force Microscopy (AFM) can be used to provide a better understanding of the mechanisms of action of these drugs at the nanoscale level on microbial interfaces. In this section, we will address these questions: (1) how does drug treatment affect the morphology of single microbes?; (2) do antimicrobial molecules modify the nanomechanical properties of microbes, or do the nanomechanical properties of microbes play a role in antimicrobial activity and efficiency?; and (3) how are the adhesive abilitites of microbes affected by antimicrobial drugs treatment? Finally, in a second part of this review we focus on recent studies aimed at changing the paradigm of the single molecule/cell technology that AFM typically represents. Recent work dealing with the creation of a microbe array which can be explored by AFM will be presented, as these developments constitute the first steps toward transforming AFM into a higher throughput technology. We also discuss papers using AFM as NanoMechnanicalSensors (NEMS), and demonstrate the interest of such approaches in clinical microbiology to detect quickly and with high accuracy microbial resistance.

Beyond the paradigm of nanomechanical measurements on cells using AFM: an automated methodology to rapidly analyse thousands of cells

“…As for the cardiology area for example cardiomyocytes are difficult to handle, and then works have reported the characterization of 1 to 30 cardiomyocytes [14][15][16][17][18][19][20] in about 6-8 h. which is a too small amount of cells to make a statistically relevant information in the context of human diseases and therefore will never be reliable enough for clinicians. Mechanical properties have also help understanding the effects of antimicrobial molecules on bacteria or yeast cell's walls 21 . Another example in the bacteria field is the work of Francius et.al 22 .…”

“…This limited number prevents the analysis of a cell population and therefore prohibits statistically relevant general conclusions or decisions. To be able to transfer the AFM technology to hospitals or pharmaceutical industry a mandatory step is to achieve high throughput results in order to analyze cell populations rather than single cells 21,31 .…”

Biomechanical Characterization at the Cell Scale: Present and Prospects

“…AFM records force-distance curves by plotting the force acting on the probe as a function of the probe-sample separation distance. Nanomechanical and nanoadhesive properties of the living material can be extracted from the experimental data by using the available physical models ( Formosa-Dague et al, 2018 ).…”

AFM and FluidFM Technologies: Recent Applications in Molecular and Cellular Biology

“…Many other achievements of AFM were realized in different fields, such as structural biology, pharmacology, and microbiology. We refer the interested readers to these valuable review articles [ 5 , 28 , 29 ].…”

“…After becoming a standard surface-imaging tool, AFM was increasingly used in biological research to investigate many properties of living cells such as electromechanical [ 3 ] and cell adhesion properties [ 4 ]. Moreover, thanks to its compatibility with aqueous environments, AFM is considered as one of the foremost tool for monitoring microbes in real time [ 5 ]. In addition, AFM provides the possibility to study biological samples under physiological conditions without extensive cell preparation.…”