Welcome to the Krell laboratory.
The Krell laboratory is part of the research group “Environmental Microbiology and Biodegradation”. The laboratory is located at the Estación Experimental del Zaidín in Granada (Spain) which is part of the Spanish National Research Council (CSIC).
An auxin controls antibiotics production in bacteria
Antibiotics production is costly to the bacterial cell and therefore in many cases subject to strict regulation. However, there is limited knowledge on the environmental cues that control antibiotics production and their corresponding mechanisms. The transcriptional regulator AdmX of the plant-associated bacterium Serratia plymuthica A153 was shown to control the synthesis of the antibiotic andrimid. AdmX contains a ligand binding domain of which we speculated to bind environmental signals that modulate its activity. Using high throughput approaches and purified protein we screened some 1700 compounds for binding and identified the auxin indole-3-acetic acid (IAA) as ligand. Antibiosis assays showed that IAA reduces andrimid production in a dose-dependent manner leading to undetectable andrimid production at 400 µM. AdmX was shown to control the transcription of the genes encoding the biosynthetic andrimid cluster. IAA is produced by plants and bacteria, and our study shows that the synthesis of IAA by other plant-associated bacteria results in the inhibition of andrimid production, suggesting that IAA bacterial production corresponds to a mode of inter-species communication.
This work provides groundbreaking insight into environmental signals that control antibiotics production and has been published as Matilla et al. in Nucleic Acids Research.
The plant compound Rosmarinic acid induces a broad quorum sensing response in Pseudomonas aeruginosa
We have shown previously that rosmarinic acid (RA) binds to the RhlR quorum sensing regulator, regulates the expression from several RhlR controlled promoters, which manifests itself in several quorum sensing (QS) related phenotypes (Corral-Lugo et al. (2016) Science Signaling 409:ra1).
In Fernández et al. (2018) Env. Microbiol. we have now assessed the global effect of RA on P. aeruginosa transcript levels using RNA-seq. RA induced the expression of 128 genes, amongst which many virulence factor genes. RA triggers a broad QS response because 88% of the induced genes are known to be controlled by QS, and because RA stimulated genes were found to be involved in all four QS signaling systems within P. aeruginosa. As shown in the Figure below there was a close overlap between RA induced genes and those induced by acylhomoserine lactone ligands.
RNA-seq results were verified by promoter expression studies using lacZ fusions. As exemplified by the hcn and lasI promoters significant induction by RA and C4-HSL was observed in the wild type (not shown) and the rhlI/lasI double mutant (below). However, no induction was observed in the rhlI/lasI/rhlR triple mutant, which is consistent with the notion that regulatory effects observed are due to the RA-RhlR interaction.
Matilla M.A., Daddaoua A., Chini A., Morel B., Krell T. (2018). An auxin controls bacterial antibiotics production. Nucleic Acids Res.
Matilla, M.A., Krell, T. (2018) The effect of bacterial chemotaxis on host infection and pathogenicity. FEMS Microbiol Rev. doi: 10.1093/femsre/fux052.
Ortega, Á., Zhulin, I.B., Krell, T. (2017) Sensory Repertoire of Bacterial Chemoreceptors. Microbiol Mol Biol Rev. doi: 10.1128/MMBR.00033-17.
Rico-Jiménez M, Reyes-Darias JA, Ortega Á, Díez Peña AI, Morel B, Krell T. (2016) Two different mechanisms mediate chemotaxis to inorganic phosphate in Pseudomonas aeruginosa. Scientific Reports 6:28967.
Corral-Lugo A, Daddaoua A, Ortega A, Espinosa-Urgel M, Krell T. (2016) Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator. Science Signaling 9(409):ra1.
Martín-Mora D, Reyes-Darias JA, Ortega A, Corral-Lugo A, Matilla MA, Krell T. (2016) McpQ is a specific citrate chemoreceptor that responds preferentially to citrate/metal ion complexes. Environ Microbiol. 18:3284-3295.
Fernández M, Morel B, Corral-Lugo A, Krell T. (2016) Identification of a chemoreceptor that specifically mediates chemotaxis toward metabolizable purine derivatives. Mol Microbiol. 99:34-42.
Reyes-Darias JA, García V, Rico-Jiménez M, Corral-Lugo A, Lesouhaitier O, Juárez-Hernández D, Yang Y, Bi S, Feuilloley M, Muñoz-Rojas J, Sourjik V, Krell T. (2015). Specific gamma-aminobutyrate (GABA) chemotaxis in Pseudomonads with different lifestyle. Mol. Microbiol. 97:488-501.
Reyes-Darias JA, Yang Y, Sourjik V, Krell T. (2015) Correlation between signal input and output in PctA and PctB amino acid chemoreceptor of Pseudomonas aeruginosa. Mol. Microbiol. 2015. 96, 513-25.
García Fontana, C., Corral-Lugo, A., Krell, T. (2014) Specificity of the CheR2 Methyltransferase in Pseudomonas aeruginosa is Directed by C-Terminal Pentapeptides in Chemoreceptors. Science Signaling 7 (320) ra34.
Garcia-Fontana C., Reyes-Darias J.A., Munoz-Martinez F., Alfonso C., Morel B., Ramos J.L., Krell T. (2013) High specificity in CheR methyltransferase function: CheR2 of Pseudomonas putida is essential for chemotaxis whereas CheR1 is involved in biofilm formation. J. Biol. Chem. 288 (26):18987-99.
Pineda-Molina, E., Reyes-Darias, J.A., Lacal, J., Ramos, J.L., García-Ruiz, J.M., Gavira, J.A., Krell, T. (2012) Evidence for chemoreceptors with bimodular ligand binding regions harboring two signal-binding sites. Proc. Acad. Natl. Sci. USA. 109, 18926-18931.