γ-butyrolactones (GBLs) are quorum sensing communication signals triggering antibiotic production. The GBL system of , the producer of the antifungal agent filipin, has been investigated. Inactivation of (for γ-utyrolactone eceptor), a GBL receptor, resulted in a strong decrease in production of filipin, and deletion of , a pseudo-receptor, boosted it, in agreement with lower and higher levels of transcription of filipin biosynthetic genes, respectively. It is noteworthy that none of the mutations affected growth or morphological development. While no ARE (autoregulatory element)-like sequences were found in the promoters of filipin genes, suggesting indirect control of production, five ARE sequences were found in five genes of the GBL cluster, whose transcription has been shown to be controlled by both SfbR and SfbR2. binding of recombinant SfbR and SfbR2 to such sequences indicated that such control is direct. Transcription start points were identified by 5' rapid amplification of cDNA ends, and precise binding regions were investigated by the use of DNase I protection studies. Binding of both regulators took place in the promoter of target genes and at the same sites. Information content analysis of protected sequences in target promoters yielded an 18-nucleotide consensus ARE sequence. Quantitative transcriptional analyses revealed that both regulators are self-regulated and that each represses the transcription of the other as well as that of the remaining target genes. Unlike other GBL receptor homologues, SfbR activates its own transcription whereas SfbR2 has a canonical autorepression profile. Additionally, SfbR2 was found here to bind the antifungal antimycin A as a way to modulate its DNA-binding activity. GBLs are important signaling molecules that trigger antibiotic production in a quorum sensing-dependent manner. We have characterized the GBL system from , finding that two key players of this system, the GBL receptor and the pseudo-receptor, each counteracts the transcription of the other for the modulation of filipin production and that such control over antifungal production involves an indirect effect on the transcription of filipin biosynthetic genes. Additionally, the two regulators bind the same sites, are self-regulated, and repress the transcription of three other genes of the GBL cluster, including that encoding the GBL synthase. In contrast to all the GBL receptors known, SfbR activates its own synthesis. Moreover, the pseudo-receptor was identified as the receptor of antimycin A, thus extending the range of examples supporting the idea of signaling effects of antibiotics in The intricate regulatory network depicted here should provide important clues for understanding the regulatory mechanism governing secondary metabolism.
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http://dx.doi.org/10.1128/AEM.00443-20 | DOI Listing |
Curr Issues Mol Biol
October 2024
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative properties. However, despite various clinical trials, scientific evidence regarding the impact on sleep of orally ingested GABA, whether natural or synthesized through biological pathways, is not clear. GABALAGEN (GBL) is the product of fermented collagen by BJ20 ( BJ20) and BJ21 ( BJ21), enriched with GABA and characterized by low molecular weight.
View Article and Find Full Text PDFMol Ther Oncol
December 2024
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Toxics
September 2024
Division of Clinical Toxicology, Poison Centre Munich, School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany.
J Immunother Cancer
June 2024
Surgery/Oncology & Microbiology/Immunology, Emory University, Atlanta, Georgia, USA
Background: How distinct methods of host preconditioning impact the efficacy of adoptively transferred antitumor T helper cells is unknown.
Methods: CD4 T cells with a transgenic T-cell receptor that recognize tyrosinase-related peptide (TRP)-1 melanoma antigen were polarized to the T helper 17 (Th17) phenotype and then transferred into melanoma-bearing mice preconditioned with either total body irradiation or chemotherapy.
Results: We found that preconditioning mice with a non-myeloablative dose of total body irradiation (TBI of 5 Gy) was more effective than using an equivalently dosed non-myeloablative chemotherapy (cyclophosphamide (CTX) of 200 mg/kg) at augmenting therapeutic activity of antitumor TRP-1 Th17 cells.
Front Microbiol
February 2024
Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
Acyl-homoserine lactones (AHLs), mediating pivotal physiological activities through quorum sensing (QS), have conventionally been considered limited to Gram-negative bacteria. However, few reports on the existence of AHLs in Gram-positive bacteria have questioned this conception. , as Gram-positive bacteria already utilizing a lactone-based QS molecule (i.
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