Speaker
Description
Unbiased and comprehensive genetic screens that are easily scalable to diverse bacterial pathogens would be valuable for obtaining a detailed understanding of antibiotic cross-resistance profiles, phage infection pathways and co-evolutionary landscapes of phage- and antibiotic resistance phenotypes. Recently, we have developed high-throughput barcoded genetic screening technologies that are scalable to different hosts; enable fast and effective genome-wide screens for gene function in competitive fitness assay format. We have applied these complementary loss-of-function and gain-of-function technologies to dozens of phages, antibiotics, metals, bacteriocins, and other antimicrobials targeting E coli, Salmonella and Pseudomonas strains. Our results accurately recapitulate known biology; identify hundreds of novel gene hits that play a role in bacterial fitness in stressful conditions; discover diverse modes of phage resistance and enable high-throughput mapping of genotype-phenotype relationships in relevant environmental conditions. By combining fitness datasets for phages, antibiotics, and antimicrobials or phage-antibiotic combination therapies, such screens could provide an avenue for performing systematic search for genetic trade-offs or ‘evolutionary traps’ and provide a much-needed solution to overcome the antibiotic-resistance pandemic.
