Abstract

The worldwide emergence of antimicrobial resistance (AMR) in pathogenic microorganisms, including bacteria and viruses due to a plethora of reasons, such as genetic mutation and indiscriminate use of antimicrobials, is a major challenge faced by the healthcare sector today. One of the issues at hand is to effectively screen and isolate resistant strains from sensitive ones. Utilizing the distinct nanomechanical properties (e.g., elasticity, intracellular turgor pressure, and Young’s modulus) of microbes can be an intriguing way to achieve this; while atomic force microscopy (AFM), with or without modification of the tips, presents an effective way to investigate such biophysical properties of microbial surfaces or an entire microbial cell. Additionally, advanced AFM instruments, apart from being compatible with aqueous environments—as often is the case for biological samples—can measure the adhesive forces acting between AFM tips/cantilevers (conjugated to bacterium/virion, substrates, and molecules) and target cells/surfaces to develop informative force-distance curves. Moreover, such force spectroscopies provide an idea of the nature of intercellular interactions (e.g., receptor-ligand) or propensity of microbes to aggregate into densely packed layers, that is, the formation of biofilms—a property of resistant strains (e.g., Staphylococcus aureus, Pseudomonas aeruginosa). This mini-review will revisit the use of single-cell force spectroscopy (SCFS) and single-molecule force spectroscopy (SMFS) that are emerging as powerful additions to the arsenal of researchers in the struggle against resistant microbes, identify their strengths and weakness and, finally, prioritize some future directions for research.

Highlights

  • The emergence of widespread antimicrobial resistance (AMR) exhibited by many commonly encountered pathogens including bacteria (e.g., Gram-positive: Staphylococcus aureus, Streptococcus pyogenes, Mycobacterium tuberculosis, and Clostridium difficile; and Gram-negative: Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Pseudomonas aeruginosa, and Neisseria gonorroheae), atomic force microscopy (AFM) in Antimicrobial Resistance viruses, and fungi (e.g., Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans) against a range of popular antimicrobials, such as blactam antibiotics, macrolides, tetracyclines, aminoglycosides, fluoroquinolones, antihelminthics, and antifungals (Singer et al, 2016; Naylor et al, 2018; Hofer, 2019; Laws et al, 2019), in both human and veterinary medicine, such as the resistance noted against ivermectin in animal husbandry (O’Shaughnessy et al, 2019), is a major challenge today

  • AMR is declared a pandemic by the World Health Organization (WHO; MacIntyre and Bui, 2017) and one of the major healthcare challenges of this century, leaving the global population vulnerable to infectious diseases (Supplementary material)

  • The role of LapA adhesin protein secreted by Pseudomonas fluorescens to enhance binding on hydrophobic surfaces was confirmed by assessing interactions between an AFM tip tethered with anti-hemagglutinin (HA) antibody and HA-tagged LapA deposited on hydrophobic alkanethiol-coated surfaces upon bacterial colonization (ElKirat-Chatel et al, 2014a; Figure 2D)

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Summary

As a Surface Mapping Tool in Microorganisms Resistant Toward

Advanced AFM instruments, apart from being compatible with aqueous environments—as often is the case for biological samples—can measure the adhesive forces acting between AFM tips/cantilevers (conjugated to bacterium/virion, substrates, and molecules) and target cells/surfaces to develop informative forcedistance curves. Such force spectroscopies provide an idea of the nature of intercellular interactions (e.g., receptor-ligand) or propensity of microbes to aggregate into densely packed layers, that is, the formation of biofilms—a property of resistant strains (e.g., Staphylococcus aureus, Pseudomonas aeruginosa).

INTRODUCTION
AFM in Antimicrobial Resistance B
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