Project description:The marine bacterium Phaeobacter inhibens produces tropodithietic acid (TDA), a broad-spectrum antibiotic and anticancer agent. TDA allows P. inhibens to antagonize other bacteria, including several pathogens, and eukaryotes. Since recently antibiotics are also discussed to function as intermicrobial signals. Here we show that ~10% of the genes of P. inhibens are strongly influenced by N-acyl-homoserine lactone (AHL) mediated quorum sensing (QS), switching the bacteriumâs life style from attached to free-living. In an AHL negative mutant of P. inhibens subinhibitory concentrations of TDA caused the same regulatory effect as the AHL. This demonstrates that bacteria can produce antibiotic compounds not only as weapons, but also to substitute their endogenous AHL molecule in QS. The dual function of TDA probably supports the QS system to accelerate regulatory processes and points to a so far neglected role of antibiotics at subinhibitory concentrations in the environment and in microbial interactions. Comparison of whole transcriptomes of wildytype, quorum sensing mutants (pgaI and pgaR) and pgaI grown supplemented with subinhibitory concentration of the antibiotic TDA. RNA isolated in the late exponential growth phase. 4 biological replicates investigated for each strain.
Project description:The marine bacterium Phaeobacter inhibens produces tropodithietic acid (TDA), a broad-spectrum antibiotic and anticancer agent. TDA allows P. inhibens to antagonize other bacteria, including several pathogens, and eukaryotes. Since recently antibiotics are also discussed to function as intermicrobial signals. Here we show that ~10% of the genes of P. inhibens are strongly influenced by N-acyl-homoserine lactone (AHL) mediated quorum sensing (QS), switching the bacterium’s life style from attached to free-living. In an AHL negative mutant of P. inhibens subinhibitory concentrations of TDA caused the same regulatory effect as the AHL. This demonstrates that bacteria can produce antibiotic compounds not only as weapons, but also to substitute their endogenous AHL molecule in QS. The dual function of TDA probably supports the QS system to accelerate regulatory processes and points to a so far neglected role of antibiotics at subinhibitory concentrations in the environment and in microbial interactions.
Project description:Quorum sensing is a term used to describe cell-to-cell communication that allows cell density-dependent gene expression. Many Gram-negative bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL quorum sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. We have discovered that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors that responds to p-coumaroyl-HSL to regulate global gene expression. We also found that p-coumaroyl-HSL is made by other bacteria including Bradyrhizobium BTAi1 and Silicibacter pomeroyi DSS-3. This discovery extends the range of possibilities for acyl-HSL quorum sensing and raises fundamental questions about quorum sensing within the context of environmental signaling. Keywords: Comparison of transcriptome profiles Transcriptome profiles between Rhodopseudomonas palustris cells grown in the in the presence or absence of pC-HSL were compared.
Project description:Drug discovery for novel anti-infectives is essential to meet the global health threat of antibiotic resistant bacterial infections, including those caused by Staphylococcus aureus1,2. Because ~90% of S. aureus infections involve skin and soft tissues (SSTIs)3,4, we hypothesized that developing anti-virulence therapeutics5,6 for SSTIs could minimize pressure on resistance development while sparing conventional antibiotics for control of systemic infections. We identified a small molecule inhibitor that disrupted signaling by a quorum sensing operon, agr, associated with human SSTIs7,8 without affecting agr-independent growth.
Project description:Quorum sensing is a term used to describe cell-to-cell communication that allows cell density-dependent gene expression. Many Gram-negative bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL quorum sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. We have discovered that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors that responds to p-coumaroyl-HSL to regulate global gene expression. We also found that p-coumaroyl-HSL is made by other bacteria including Bradyrhizobium BTAi1 and Silicibacter pomeroyi DSS-3. This discovery extends the range of possibilities for acyl-HSL quorum sensing and raises fundamental questions about quorum sensing within the context of environmental signaling. Keywords: Comparison of transcriptome profiles
Project description:The Pseudomonas synxantha strain NCIMB10586 produces the antibiotic mupirocin / Pseudomonic acid A from a 75 kb gene cluster; expression of this is regulated through quorum-sensing. We wished to examine expression of the strain during batch growth, in particular of the mupirocin cluster and any other operons regulated in a similar manner. We took samples from three independent cultures at 7 time-points - sampling every 2 hours from 6 to 18 hours.
