Cyclic di-GMP-Dependent Regulation of Antibiotic Biosynthesis in Lysobacter
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Lysobacter enzymogenes is an environmental bacterium that secrets a heat-stable antifungal factor, HSAF, an antibiotic against crop fungal pathogens. Elevated levels of cyclic di-GMP inhibit HSAF synthesis. The transcription factor cAMP receptor-like protein Clp binds to two sites upstream of the promoter of the HSAF biosynthesis operon and activates gene expression. At elevated cyclic di-GMP levels, cyclic di-GMP binding to Clp compromises binding to DNA, particularly at the low-affinity binding site, which results in lower expression of the HSAF biosynthesis operon. Two cyclic di-GMP phosphodiesterases contribute the most to cyclic di-GMP-dependent regulation of HSAF production. One of them, the GGDEF-EAL protein, LchP, forms a protein complex with Clp. Such specificity of targeted action allows LchP that has relatively weak phosphodiesterase activity, to play an oversized role in Clp-dependent HSAF biosynthesis. The HD-GYP phosphodiesterase RpfG is another major phosphodiesterase, whose activity is increased at higher cell density via a quorum-sensing mechanism. Further, a common regulator of type IV pilus synthesis, PilR, modulates HSAF biosynthesis via an as yet uncharacterized cyclic di-GMP signaling pathway. These findings represent novel insights into cyclic di-GMP-dependent antibiotic biosynthesis regulation in an agriculturally important bacterium.
KeywordsLysobacter Cyclic di-GMP Phosphodiesterase Diguanylate cyclase HSAF Cyclic di-GMP-binding receptor
This study was supported by the Natural Science Foundation of Jiangsu Province (BK20190026; BK20181325 to GQ), the Fundamental Research Funds for the Central Universities (KJJQ202001; KYT201805 and KYTZ201403 to GQ), National Natural Science Foundation of China (31872016 and 31572046 to GQ) and National Basic Research (973) Program of China (2015CB150600 to GQ). Shan-Ho Chou was supported by the MoST grant of Taiwan (105-2113-M-005-013-MY2). Mark Gomelsky was supported by US National Institutes of Health (R21 AI135683-01).
Conflict of Interest Statement
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