Force nanoscopy in microbiology

Microbial cells have developed sophisticated multicomponent structures and machineries to control cellular processes, such as cell division and biofilm formation. A current challenge in molecular microbiology is to understand how these cellular structures assemble and interact to achieve their functions.

Live-cell nanoscopy: imaging and manipulating cells on the nanoscale
Recent progress in live-cell nanoscopy has offered new tools to probe living cells at the single-molecule and single-cell levels. We are applying atomic force microscopy (AFM) techniques to address fundamental problems in microbiology that are impossible or difficult to solve with traditional approaches. The strategy involves developing single-molecule and single-cell AFM methods (cell preparation and tip functionalization, high-resolution imaging, single-molecule and single-cell force spectroscopy, recognition imaging), and combining these tools with fluorescence and microbiology approaches to address the cell surface. Over the years, these innovative tools have enabled us to understand how cell surface constituents are spatially organized and how they interact with their environment. These achievements have been made possible owing to successful collaborations with microbiologists. We share facilities and staff with the Alsteens team.

Staphylococcal biofilms: mechanisms and inhibition
We are currently putting much effort into the development of an innovative nanoscopy platform to challenge our understanding of biofilm formation by microbial pathogens, and to optimize the use of anti-adhesin compounds (antibodies, peptides) targeting these biofilms.

Staphylococcus aureus is a leading cause of hospital-acquired infections, which are often complicated by the ability of this pathogen to grow as biofilms.on indwelling medical devices. Because biofilms protect the bacteria from host defenses and are resistant to many antibiotics, biofilm-related infections are difficult to fight and represent a tremendous burden on our healthcare system. A molecular understanding of the fundamental interactions driving staphylococcal adhesion and biofilm formation will greatly contribute to the development of novel anti-adhesion therapies for combating biofilm infections.

Further reading
Xiao, J. and Dufrêne, Y.F. (2016) Optical and force nanoscopy in microbiology. Nat. Microbiol., 1:16186.
Dufrêne, Y.F. (2014) Atomic force microscopy in microbiology: new structural and functional insights into the microbial cell surface. mBio, 5:e01363-14.
Müller, D.J., Helenius, J., Alsteens, D. and Dufrêne Y.F. (2009) Force probing surfaces of living cells to molecular resolution. Nat. Chem. Biol. 5, 383-390.
Dufrêne, Y.F. (2008) Towards nanomicrobiology using atomic force microscopy. Nature Rev. Microbiol. 6, 674-680.