Infection-Mimetic Screening for Antimicrobial Target Discovery
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Solution Overview
Problem
Current in vitro screening methods for antimicrobial and antiproliferative compounds are optimized for rapid growth conditions, failing to account for the stress and nutrient limitations encountered by pathogens in vivo, leading to the missed identification of important drug targets and compounds.
Innovation Solution
Grow fungal and bacterial cells under infection mimetic conditions to identify differentially regulated genes, and screen compounds for activity in these conditions, as well as in clinical samples mimicking infection sites, to identify effective antimicrobial compounds, and grow mammalian cancer cells under cancer mimetic conditions to identify antiproliferative compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If in vitro screening is performed under standard laboratory conditions optimized for rapid growth, then screening efficiency and speed are improved, but the ability to identify drug targets and compounds effective against pathogens in vivo is worsened
Solution Approach 1:
The patent changes the growth conditions parameters from standard laboratory conditions to infection mimetic conditions, including nutrient limitation, stress conditions, and reduced growth rates, to better reflect in vivo pathogen environment and identify compounds that work effectively under these conditions
Solution Approach 2:
The patent creates in vitro infection mimetic conditions that copy or replicate the in vivo infection environment, allowing screening of compounds under conditions that mimic the actual pathogen habitat and host interactions
2Reliability
If in vitro screening is performed under infection mimetic conditions, then the identification of effective antimicrobial compounds is improved, but screening time and complexity are worsened
Solution Approach 1:
The patent performs preliminary characterization of pathogens under infection mimetic conditions to identify key physiological states and gene expression patterns before conducting compound screening, allowing for more targeted and efficient compound evaluation
3Ease of operation
If standard in vitro screening methods are used, then ease of operation is improved, but the ability to detect drug targets regulated under infection conditions is worsened
Solution Approach 1:
The patent dynamically adjusts screening conditions to match the dynamic physiological state of pathogens during infection, including nutrient availability, stress responses, and growth rates, rather than using static standard laboratory conditions
Solution Approach 2:
The patent incorporates feedback mechanisms where gene expression data from infection mimetic conditions is used to identify and prioritize drug targets, and compound screening results are fed back to refine understanding of pathogen physiology and target validation
Data Source
AI summary
The invention is directed to methods for identifying targets for antimicrobial and antiproliferative compounds as well as methods for identifying novel compounds for treating cancer and microbial infections.