title: Small-molecule inhibitors suppress the expression of both type III secretion and amylovoran biosynthesis genes in Erwinia amylovora.
abstract: The type III secretion system (T3SS) and exopolysaccharide (EPS) amylovoran are two essential pathogenicity factors in Erwinia amylovora, the causal agent of the serious bacterial disease fire blight. In this study, small molecules that inhibit T3SS gene expression in E. amylovora under hrp (hypersensitive response and pathogenicity)-inducing conditions were identified and characterized using green fluorescent protein (GFP) as a reporter. These compounds belong to salicylidene acylhydrazides and also inhibit amylovoran production. Microarray analysis of E. amylovora treated with compounds 3 and 9 identified a total of 588 significantly differentially expressed genes. Among them, 95 and 78 genes were activated and suppressed by both compounds, respectively, when compared with the dimethylsulphoxide (DMSO) control. The expression of the majority of T3SS genes in E. amylovora, including hrpL and the avrRpt2 effector gene, was suppressed by both compounds. Compound 3 also suppressed the expression of amylovoran precursor and biosynthesis genes. However, both compounds induced significantly the expression of glycogen biosynthesis genes and siderophore biosynthesis, regulatory and transport genes. Furthermore, many membrane, lipoprotein and exported protein-encoding genes were also activated by both compounds. Similar expression patterns were observed for compounds 1, 2 and 4. Using crab apple flower as a model, compound 3 was capable of reducing disease development in pistils. These results suggest a common inhibition mechanism shared by salicylidene acylhydrazides and indicate that small-molecule inhibitors that disable T3SS function could be explored to control fire blight disease.
authors.affiliation: Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Schuyler S
authors.initials: SS
authors.lastname: Korban
authors.forename: P Lawrence
authors.initials: PL
authors.lastname: Pusey
authors.forename: Michael
authors.initials: M
authors.lastname: Elofsson
authors.forename: George W
authors.initials: GW
authors.lastname: Sundin
authors.forename: Youfu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D058947:Bacterial Secretion Systems / Q000187:drug effects / Q000235:genetics*; D053898:Biosynthetic Pathways / Q000187:drug effects / Q000235:genetics*; D018450:Disease Progression; D044084:Erwinia amylovora / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D035264:Flowers / Q000187:drug effects / Q000382:microbiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000235:genetics*; D027845:Malus / Q000187:drug effects / Q000382:microbiology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010935:Plant Diseases / Q000235:genetics / Q000382:microbiology; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D058947:Bacterial Secretion Systems; D011135:Polysaccharides, Bacterial; D054852:Small Molecule Libraries; C100769:amylovoran
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