Abstract
Microbes have an arsenal of virulence factors that contribute to their pathogenicity. A number of challenges remain to fully understand disease transmission, fitness landscape, antimicrobial resistance and host heterogeneity. A variety of tools have been used to address diverse aspects of pathogenicity, from molecular host-pathogen interactions to the mechanisms of disease acquisition and transmission. Current gaps in our knowledge include a more direct understanding of host-pathogen interactions, including signaling at interfaces, and direct phenotypic confirmation of pathogenicity. Correlative microscopy has been gaining traction to address the many challenges currently faced in biomedicine, in particular the combination of optical and atomic force microscopy (AFM). AFM, generates high-resolution surface topographical images, and quantifies mechanical properties at the pN scale under physiologically relevant conditions. When combined with optical microscopy, AFM probes pathogen surfaces and their physical and molecular interaction with host cells, while the various modes of optical microscopy view internal cellular responses of the pathogen and host. Here we review the most recent advances in our understanding of pathogens, recent applications of AFM to the field, how correlative AFM-optical microspectroscopy and microscopy have been used to illuminate pathogenicity and how these methods can reach their full potential for studying host-pathogen interactions.
Highlights
Relevance of PathogensDespite tremendous progress in global health initiatives, the world continues to be confronted by infectious disease, underscoring the need for their survey, prevention, containment and treatment (Bloom and Cadarette, 2019)
Unlike optical and electron microscopy (EM), atomic force microscopy (AFM) scans a cantilever-mounted tip over the sample surface, with tip-sample forces used for feedback control of piezoelectric micropositioners required to contour the biological specimen
The power of AFM is enhanced when used in combination with other techniques capable of biochemical mapping, and is complementary to traditional molecular genetics methods to study pathogens
Summary
Despite tremendous progress in global health initiatives, the world continues to be confronted by infectious disease, underscoring the need for their survey, prevention, containment and treatment (Bloom and Cadarette, 2019). Despite significant AMR research, we are far from understanding the associated mechanisms. Climate change, causing increased environmental fluctuations, has led to the emergence and re-emergence of pathogens, Correlative Microscopy in Pathogen Research further reinforcing the need for developing strategies to reduce the burden of infectious diseases (Gudipati et al, 2020). Vast technological developments over the past-decade in next-generation sequencing and proteomics have helped delineate the genetics of pathogenicity and mechanisms of host-pathogen interactions at the molecular level, respectively (Maljkovic Berry et al, 2020; Rauwane et al, 2020). One of the biggest gaps in our understanding of host invasion by pathogens is the accompanying physiological changes, especially during the initial stages of colonization and invasion, which can be viewed and measured using microscopic methods
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