Diaphorin induces extensive transcriptional remodeling of translation, transport, metabolism, and stress responses in Escherichia coli

Abstract

Diaphorin is a pederin-family polyketide produced by the obligate bacterial symbiont "Candidatus Profftella armatura" (Betaproteobacteria) of the Asian citrus psyllid Diaphorina citri, in which it accumulates at millimolar concentrations. Diaphorin suppresses the growth of many bacterial species but promotes the growth and metabolic activity of Escherichia coli, highlighting the importance of elucidating the mechanisms underlying these contrasting effects. Although cell-free studies show that diaphorin directly affects bacterial translation, how E. coli transcription changes during growth promotion remains unclear. Here, we analyzed the transcriptome of E. coli after 7 h of exposure to 5 mM diaphorin, when its growth-promoting effect is most pronounced. Diaphorin altered the expression of 1,278 of 4,269 analyzed genes. Functional enrichment analyses revealed strong negative enrichment of translation- and ribosome-related functions, pathway-specific changes in metabolism, and enrichment of transport-, stress-response, and quorum-sensing-related functions. Ribosomal protein genes were broadly downregulated, whereas coordinated upregulation was observed in mdtEF, prpBCDE, the Gad system, and luxS/lsr genes. These findings indicate functionally structured transcriptional remodeling during diaphorin-enhanced growth. Together with previous cell-free evidence, the pronounced translation-related changes observed here highlight bacterial translation as a major process associated with the response of E. coli to diaphorin. One possible interpretation of the apparently contrasting observations is that an earlier stimulation of bacterial translation is followed by compensatory downregulation of translation-related genes as growth proceeds. More broadly, these transcriptional changes provide insight into diaphorin-enhanced growth in E. coli and offer a basis for understanding the strikingly different effects of this symbiont-derived polyketide among bacterial species.