Wisdom of the crowds: A suggested polygenic plan for small-RNA-mediated regulation in bacteria.

The omnigenic/polygenic theory, which states that complex traits are not shaped by single/few genes, but by situation-specific large networks, offers an explanation for a major enigma in microbiology: deletion of specific small RNAs (sRNAs) playing key roles in various aspects of bacterial physiology, including virulence and antibiotic resistance, results in surprisingly subtle phenotypes. A recent study uncovered polar accumulation of most sRNAs upon osmotic stress, the majority not known to be involved in the applied stress. Here we show that cells deleted for a handful of pole-enriched sRNAs exhibit fitness defect in several stress conditions, as opposed to single, double, or triple sRNA-knockouts, implying that regulation by sRNA relies on sets of genes. Moreover, analysis of RNA-seq data of Escherichia coli and Salmonella typhimurium exposed to antibiotics and/or infection-relevant conditions reveals the involvement of multiple sRNAs in all cases, in line with the existence of a polygenic plan for sRNA-mediated regulation.