Abstract
In plants, cellulose biosynthesis is an essential process for anisotropic growth and therefore is an ideal target for inhibition. Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted by acetobixan, suggesting specific activity towards cellulose synthesis. Previous CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant to acetobixan indicating that acetobixan targets a different aspect of cellulose biosynthesis.
Highlights
Active small molecules are extremely useful tools that facilitate the dissection of cellular pathways in a manner that is often unattainable by genetic methods
Identification of indexed bacterial endophytes capable of inhibiting cellulose biosynthesis Cross-kingdom signaling between endophytes and the plant host has been demonstrated to depend on small molecules in some systems [44]
Since the cell wall represents a key barrier to the entry of endophytic microorganisms into the plant, it is plausible that some endophytic species may secrete small molecules that reversibly inhibit the synthesis of cell wall polysaccharides to temporarily weaken the cell wall and facilitate microbial entry
Summary
Active small molecules are extremely useful tools that facilitate the dissection of cellular pathways in a manner that is often unattainable by genetic methods. The capacity to identify synthetic bioactive compounds has been aided by advancements in high-throughput screening platforms as well as combinatorial chemical libraries [1] These approaches have been employed by a community of researchers to identify compounds that interfere with plant metabolic processes [2,3,4,5,6,7], signal transduction pathways [8,9,10,11,12], and vesicle trafficking events [13,14,15]. Identification of useful lead compounds from complex biological samples remains challenging due to the fact that bioactive small molecules must be purified away from numerous compounds that do not confer the activity of interest
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
