The geographical region of origin determines the phagocytic vulnerability of Lichtheimia strains

Abstract

Summary Mucormycoses are life‐threatening infections that affect patients suffering from immune deficiencies. We performed phagocytosis assays confronting various strains of Lichtheimia species with alveolar macrophages, which form the first line of defence of the innate immune system. To investigate 17 strains from four different continents in a comparative fashion, transmitted light and confocal fluorescence microscopy was applied in combination with automated image analysis. This interdisciplinary approach enabled the objective and quantitative processing of the big volume of image data. Applying machine‐learning supported methods, a spontaneous clustering of the strains was revealed in the space of phagocytic measures. This clustering was not driven by measures of fungal morphology but rather by the geographical origin of the fungal strains. Our study illustrates the crucial contribution of machine‐learning supported automated image analysis to the qualitative discovery and quantitative comparison of major factors affecting host–pathogen interactions. We found that the phagocytic vulnerability of Lichtheimia species depends on their geographical origin, where strains within each geographic region behaved similarly, but strongly differed amongst the regions. Based on this clustering, we were able to also classify clinical isolates with regard to their potential geographical origin.

Comparative immunopathogenesis in a murine model of inhalative infection with the mucormycetes Lichtheimia corymbifera and Rhizopus arrhizus

“…Since our experiments include a large variety of different experimental conditions and animal groups, insights about the intraspecies heterogeneity have to remain limited also in the future due to ethical reasons. Other reports support the hypothesis of heterogeneity in virulence and phagocytic vulnerability [27,28] and imply that the geographical origin of the isolates might play a substantial role. In summary, mucormycosis appears to be a very heterogeneous disease, and a lot of scientific research remains to be done for a deeper insight of interactions of the various fungal agents and isolates with the host defense, which will be a vital prerequisite for new therapeutic options.…”

Enhanced segmentation of label‐free cells for automated migration and interaction tracking

“…In the future, this feature needs to be extended for studies of interactions between immune cells and pathogens, because the qualitative and quantitative impact of labeling cell membranes was recently shown in the context of host‐pathogen interactions [4]. While this analysis was done only for endpoint images of phagocytosis assays, we expect that a segmentation approach similar to the Hessian‐based filtering [28], which has been shown to be successful in large‐scale phagocytosis studies [29], can also be applied to host‐pathogen interaction dynamics in AMIT. Another option for tracking host‐pathogen interactions in a label‐free manner may be pursued by the application of deep learning methods.…”

Discovery of a New Lichtheimia (Lichtheimiaceae, Mucorales) from Invertebrate Niche and Its Phylogenetic Status and Physiological Characteristics

“…The genus Lichtheimia ( Mucorales , Lichtheimiaceae ) consists of saprotrophic fungi inhabiting soil, plants, indoor air, food products, and feces [ 1 , 7 , 8 ] and contains important causative agents of mucormycoses in humans and animals [ 7 , 9 ]. Species of Lichtheimia are broadly distributed in all continents, with species being isolated from environmental and clinical sources [ 6 , 9 , 10 ].…”