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).
Understanding how new chemoreceptors evolve
Many bacteria possess a large number of chemoreceptors that each respond to different signal molecules and frequently genomes contain paralogous receptors that have arisen by gene duplication. We have studied chemoreceptor evolution using the three paralogous receptors PctA, PctB and PctC of Pseudomonas aeruginosa as examples. Whereas PctA is a broad range receptor that responds to most proteinogenic amino acids, PctB and PctC recognize preferentially L-Gln and GABA, respectively. In a stimulating collaboration with the laboratory of Igor Zhulin (Ohio State University) we show that pctA gene duplication in the common ancestor of the genus Pseudomonas led to pctC, whereas pctB originated through another, independent pctA duplication in the common ancestor of P. aeruginosa. The 3D structures of the ligand binding domains of these three receptors in complex with several ligands were solved in an excellent collaboration with the laboratory of Jose A. Gavira and reveal the structural basis for differential ligand recognition.
Identification of the molecular basis of nitrate chemotaxis
Nitrate is of central relevance in bacterial physiology and it is known for a long time that many bacteria are able to perform taxis towards nitrate. So far, data suggest that these movements are based on energy tactic mechanisms in which metabolic consequences of nitrate metabolism are monitored. In this article we report a mechanism for nitrate chemotaxis that is based on the specific recognition of this ligand by the periplasmatic PilJ-type sensor domain of the McpN chemoreceptor of Pseudomonas aeruginosa. Nitrate chemotaxis occurred only under nitrate limiting condition, an observation that is most likely due to the nitrate-mediated reduction of mcpN transcript levels. We report the 3D structure of the McpN sensor domain in complex with nitrate at a resolution of 1.3 Å in which one nitrate molecule was bound at the dimer interface. McpN homologues were identified in many bacteria and were particularly abundant in species that couple sulfur/sulfite oxidation with nitrate reduction. Nitrate chemotaxis is likely to be a widespread phenomenon with importance for the life cycle of ecologically diverse bacteria.
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.
Bacterial chemotaxis to histamine
Histamine is a key signal molecule that coordinates the immune response. Previous studies have shown that the infection with the human pathogen Pseudomonas aeruginosa increases histamine secretion by neutrophils. In our article Corral-Lugo et al. (2018) mbio 9, e01894-18 we demonstrate that P. aeruginosa shows high-sensitivity chemotactic responses to histamine. These responses are primarily mediated by the TlpQ chemoreceptor that binds histamine with nanomolar affinity. The three-dimensional structure of the TlpQ ligand binding domain reveals that it is a dCACHE domain that contains bound histamine in its membrane distal module. Histamine chemotaxis is likely to play a role in bacterial virulence since it will induce bacterial migration to infection sites. This in turn alters the local bacterial quorum, causing a modulation of the expression of quorum sensing controlled virulence genes
Gavira JA, Gumerov VM, Rico-Jiménez M, Petukh M, Upadhyay AA, Ortega A, Matilla MA, Zhulin IB, Krell T. (2020) How Bacterial chemoreceptors evolve novel ligand specificities. mBio 11, e03066-19.
Martín-Mora, D., Ortega, A., Matilla, M.A., Martínez-Rodríguez, S., Gavira, J.A., Krell, T. (2019) The molecular mechanism of nitrate chemotaxis via direct ligand binding to the PilJ domain of McpN. mBio 10, e02334-18
Corral-Lugo A., Matilla M.A., Martín-Mora D., Silva Jiménez H., Mesa Torres N., Kato J., Hida A., Oku S., Conejero-Muriel M., Gavira J.A., Krell T. (2018). High-affinity chemotaxis to histamine mediated by the TlpQ chemoreceptor of the human pathogen Pseudomonas aeruginosa. mBio 9, e01894-18
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.
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.