Abstract
Clostridium difficile infection (CDI) is an increasing global health threat and major worldwide cause of hospital-acquired diarrhea. The development of novel therapies to effectively treat this bacterial pathogen is an unmet clinical need. Here, we describe an image processing and classification algorithm that automatically identifies toxin-induced cytotoxicity to host cells based on characteristic morphological changes. This efficient and automatic algorithm can be incorporated into a screening platform to identify novel anti-toxin inhibitors of the C. difficile major virulence factors TcdA and TcdB, and contains the following steps: image enhancement, cell segmentation, and classification. We tested the algorithm on 504 images (containing 5096 cells) and achieved 93% sensitivity and 91% specificity, indicating that the proposed computational approach correctly classified most of the cells and provided reliable information for an effective screening platform. This algorithm achieved higher classification results compared to existing cell counter and analysis programs, scoring 92.6% accuracy. Compared to visual examination by a researcher, the algorithm significantly decreased classification time and identified toxin-induced cytotoxicity in an unbiased manner. Availability: Examples are available at home.agh.edu.pl/jaworek/CDI.
Highlights
Clostridium difficile infection (CDI) is an increasing global health threat and major cause of hospital-acquired diarrhea [1,2,3]
An alternative therapeutic strategy to antibiotic treatment is the development of anti-toxin compounds that neutralize the toxin mediators of disease—toxins A and B (TcdA and TcdB) of C. difficile [6]
Sci. 2018, 8, 1512 based on image processing and classification algorithms to rapidly screen and identify anti-toxin inhibitors of TcdA and TcdB activity based on characteristic morphological changes to host cells upon toxin-mediated cytotoxicity
Summary
Clostridium difficile infection (CDI) is an increasing global health threat and major cause of hospital-acquired diarrhea [1,2,3]. An alternative therapeutic strategy to antibiotic treatment is the development of anti-toxin compounds that neutralize the toxin mediators of disease—toxins A and B (TcdA and TcdB) of C. difficile [6]. Sci. 2018, 8, 1512 based on image processing and classification algorithms to rapidly screen and identify anti-toxin inhibitors of TcdA and TcdB activity based on characteristic morphological changes to host cells upon toxin-mediated cytotoxicity.
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