Systems-level interference strategies to decipher host factors involved in bacterial pathogen interaction: from RNAi to CRISPRi

•Systems level approaches aim at comprehensively accessing pathogen-host interaction.•High quality genome-wide datasets are required for these approaches.•New solutions are deployed to circumvent OTE in RNAi-based screens.•CRISPR/Cas methodologies offer promising alternatives or complementary readouts.

Bacterial pathogen-host cell interactions involve an intricate interplay of multiple components from both partners. Systems level surveys have been used widely to profile host requirements for pathogen infection. Functional genomics, and more specifically genome-wide perturbation screens, constitute attractive methodologies to assess such host infectomes. Although these strategies have successfully identified numerous critical host factors, they may have failed in generating the high-quality data required for systems level analysis. This is the case for most RNA interference (RNAi) setups with their high propensity to off-target effects (OTE). However, recent efforts to circumvent OTE in RNAi-based experiments as well as the emergence of alternative strategies will likely soon allow significant breakthrough in the systems level understanding of bacterial pathogen-host interactions.

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