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Laboratory-based evolution and whole-genome sequencing can link genotype and phenotype. We used evolution of acid resistance in exponential phase Escherichia coli to study resistance to a lethal stress. Iterative selection at pH 2.5 generated five populations that were resistant to low pH in early exponential phase. Genome sequencing revealed multiple mutations, but the only gene mutated in all strains was evgS, part of a two-component system that has already been implicated in acid resistance. All these mutations were in the cytoplasmic PAS domain of EvgS, and were shown to be solely responsible for the resistant phenotype, causing strong upregulation at neutral pH of genes normally induced by low pH. Resistance to pH 2.5 in these strains did not require the transporter GadC, or the sigma factor RpoS. We found that EvgS-dependent constitutive acid resistance to pH 2.5 was retained in the absence of the regulators GadE or YdeO, but was lost if the oxidoreductase YdeP was also absent. A deletion in the periplasmic domain of EvgS abolished the response to low pH, but not the activity of the constitutive mutants. On the basis of these results we propose a model for how EvgS may become activated by low pH.

Endophytes represent a ubiquitous and magical world in plants. Almost all plant species studied by different researchers have been found to harbor one or more endophytes, which protect host plants from pathogen invasion and from adverse environmental conditions. They produce various metabolites that can directly inhibit the growth of pathogens and even promote the growth and development of the host plants. In this review, we focus on the biological control of plant diseases, aiming to elucidate the contribution and key roles of endophytes and their metabolites in this field with the latest research information. Metabolites synthesized by endophytes are part of plant disease management, and the application of endophyte metabolites to induce plant resistance is very promising. Furthermore, multi-omics should be more fully utilized in plant–microbe research, especially in mining novel bioactive metabolites. We believe that the utilization of endophytes and their metabolites for plant disease management is a meaningful and promising research direction that can lead to new breakthroughs in the development of more effective and ecosystem-friendly insecticides and fungicides in modern agriculture.

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