Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

作者:Babu Mohan*; Diaz Mejia J Javier; Vla**lom James; Gagarinova Alla; Phanse Sadhna; Graham Chris; Yousif Fouad; Ding Huiming; Xiong Xuejian; Nazarians Armavil Anaies; Alamgir Md; Ali Mehrab; Pogoutse Oxana; Pe'er Asaf; Arnold Roland; Michaut Magali; Parkinson John; Golshani Ashkan; Whitfield Chris; Wodak Shoshana J; Moreno Hagelsieb Gabriel; Greenblatt Jack F; Emili Andrew
来源:PLoS Genetics, 2011, 7(11): e1002377.
DOI:10.1371/journal.pgen.1002377

摘要

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.