Heat-Stable Antifungal Factor (HSAF) Biosynthesis in Lysobacter enzymogenes Is Controlled by the Interplay of Two Transcription Factors and a Diffusible Molecule

• Published in: Applied and environmental microbiology Vol. 84; no. 3
• Main Authors: Su, Zhenhe, Han, Sen, Fu, Zheng Qing, Qian, Guoliang, Liu, Fengquan
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.02.2018
• Subjects: Anti-Bacterial Agents - metabolism; Antibiotics; Antifungal Agents - metabolism; Bacteria; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biosynthesis; Diffusion; Environmental Microbiology; Fungicides; Gene expression; Gene Expression Regulation, Bacterial; Gene regulation; Hot Temperature; Lysobacter - genetics; Lysobacter - metabolism; Molecules; p-Hydroxybenzoic acid; Parabens - metabolism; Proteins; Signal Transduction; Thermal stability; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; MarR; HSAF; 4-HBA; Lysobacter
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/aem.01754-17

is a Gram-negative, environmentally ubiquitous bacterium that produces a secondary metabolite, called heat-stable antifungal factor (HSAF), as an antifungal factor against plant and animal fungal pathogens. 4-Hydroxybenzoic acid (4-HBA) is a newly identified diffusible factor that regulates HSAF synthesis via LysR (LysR ), an LysR-type transcription factor (TF). Here, to identify additional TFs within the 4-HBA regulatory pathway that control HSAF production, we reanalyzed the LenB2-based transcriptomic data, in which LenB2 is the enzyme responsible for 4-HBA production. This survey led to identification of three TFs (Le4806, Le4969, and Le3904). Of them, LarR (Le4806), a member of the MarR family proteins, was identified as a new TF that participated in the 4-HBA-dependent regulation of HSAF production. Our data show the following: (i) that LarR is a downstream component of the 4-HBA regulatory pathway controlling the HSAF level, while LysR is the receptor of 4-HBA; (ii) that 4-HBA and LysR have opposite regulatory effects on transcription whereby transcript is negatively modulated by 4-HBA while LysR , in contrast, exerts positive transcriptional regulation by directly binding to the promoter without being affected by 4-HBA ; (iii) that LarR, similar to LysR , can bind to the promoter of the HSAF biosynthetic gene operon, leading to positive regulation of HSAF production; and (iv) that LarR and LysR cannot interact and instead control HSAF biosynthesis independently. These results outline a previously uncharacterized mechanism by which biosynthesis of the antibiotic HSAF in is modulated by the interplay of 4-HBA, a diffusible molecule, and two different TFs. Bacteria use diverse chemical signaling molecules to regulate a wide range of physiological and cellular processes. 4-HBA is an "old" chemical molecule that is produced by diverse bacterial species, but its regulatory function and working mechanism remain largely unknown. We previously found that 4-HBA in could serve as a diffusible factor regulating HSAF synthesis via LysR Here, we further identified LarR, an MarR family protein, as a second TF that participates in the 4-HBA-dependent regulation of HSAF biosynthesis. Our results dissected how LarR acts as a protein linker to connect 4-HBA and HSAF synthesis, whereby LarR also has cross talk with LysR Thus, our findings not only provide fundamental insight regarding how a diffusible molecule (4-HBA) adopts two different types of TFs for coordinating HSAF biosynthesis but also show the use of applied microbiology to increase the yield of the antibiotic HSAF by modification of the 4-HBA regulatory pathway in .