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). The Krell laboratory participates in the Master “Investigation and Advances in Microbiology” (https://masteres.ugr.es/microbiologia/) at Granada University.


The stunning pH robustness of extracytosolic bacterial sensor domains

Monteagudo-Cascales et al. (2022) mBio e0165022

Signal transduction is typically initiated by the recognition of signal molecules at receptor sensor domains. Hundreds of different types of sensor domains have evolved. In this article we have investigated the capacity of members of the four major superfamilies of extracytosolic sensor domains to recognize their signals at different pH. We have furthermore analysed the pH dependence of signal recognition of periplasmic solute binding proteins as well as cytosolic sensor domains. We show that extracytosolic sensor domains possess a stunning pH robustness, which is exemplified by the sensor domains of the Tar and PctA chemoreceptors that recognized their cognate signals over 7.5 and 8.5 pH units, respectively. A similar pH robustness was observed for periplasmic solute binding proteins, whereas cytosolic sensor domains bound their ligands over a much narrower pH range. Data thus suggest that many receptors maintain their sensing capacities over a broad range permitting in turn signal integration under harsh environmental conditions. These data also permit the construction of robust biosensors.

The importance of amino acid sensing for living beings

Gumerov et al. (2022) Proc. Natl. Acad. Sci. USA 119, e2110415119

Organisms throughout the Tree of Life possess the capacity to sense extracellular signals and to adjust a variety of physiological features in response. In this article we discover an extracellular sensing domain, termed dCache_1AA, that recognizes specifically amino acids. This domain is found in archaea, bacteria and different eukaryotes including the human, illustrating the importance of amino acid sensing throughout the Tree of Life. In bacteria, dCache_1AA domains are found in all major families of transmembrane signal transduction receptors including chemoreceptors, sensor histidine kinases, guanylate/adenylate cyclases, c-di-GMP phosphodiesterases or serine/threonine kinases and phosphatases, which underlines its universality. This study has also demonstrated the feasibility of predicting the ligands recognized by sensor domains taking into account the amino acids present in the ligand binding pocket.

A bacterial chemoreceptor for the neurotransmitter acetylcholine

Matilla et al. (2022) mBio e0345821

There is doubt that that the chemosensory capacity of a bacterium is a reflection of its lifestyle. However, a more detailed understanding on the chemoeffectors perceived by bacteria with a given lifestyle is still missing. In this publication we show that the human pathogen Pseudomonas aeruginosa shows strong chemoattraction towards acetylcholine, a central neurotransmitter in human. Acetylcholine was found to bind to the dCache type sensor domain of the PctD chemoreceptor. To determine the molecular determinants of acetylcholine recognition we report the high-resolution structures of the PctD sensor domain in complex with acetylcholine and that of the homologous PacA chemoreceptor that is unable to recognize acetylcholine. Interestingly, in previous studies, Reyes-Darias et al. (2015) and Corral-Lugo et al. (2018) we have identified two other P. aeruginosa chemoreceptors, PctC and TlpQ, that recognize the neurotransmitters GABA and histamine, suggesting a particular relevance of neurotransmitter chemotaxis in P. aeruginosa. This study expands the range of biologically relevant signal molecules that are perceived as chemoattractants by bacteria.

A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators

Matilla et al. (2021) FEMS Microbiol Rev. 10.1093/femsre/fuab043.

We have compiled a catalogue of 1750 interactions of signal molecules with the three major super-families of bacterial signal transduction proteins, namely sensor kinases, chemoreceptors and transcriptional regulators. These proteins recognize signal molecules typically at their sensor or ligand-binding domain. Data were extracted manually from about 1200 articles and the protein data bank. This catalogue contains 811 proteins. Importantly, only data showing direct interactions were considered and indirect evidence such as in vivo gene expression in the presence of signal molecules were not included. Proteins were classified according to the Pfam family of their respective sensor domains into 127 groups. This work reveals the signal binding characteristics of a large part of bacterial sensor domains. Whereas some sensor domains showed significant promiscuity in signal recognition, other domains were found to possess a well-defined signal profile. The lacking knowledge of the signal molecules that active bacterial signal transduction systems is a major bottle neck in microbiology and this work will facilitate the identification of signals that bind to homologous but uncharacterized sensor proteins.

Review article on chemosensory pathways with different function

Matilla et al. (2021) Microbiol. Mol. Biol. Rev. 85(1):e00151-20

Pseudomonas aeruginosa has 26 chemoreceptors that stimulate in total four different chemosensory pathways. These pathways differ in function: The che pathway mediates chemotaxis, the wsp pathway modulates c-di-GMP levels, the chp pathway is associated with type IV pili based motility and cAMP levels, whereas the function of the che2 pathways is unknown. To some extent all pathways are involved in virulence. There is now a large body of information available on these pathways making P. aeruginosa a convenient model organism. We have reviewed these data and hope this is of help to the scientific community.


Selected publications

Monteagudo-Cascales, E., Martín-Mora, D., Xu, W., Sourjik, V., Matilla, M.A. Ortega, A., Krell, T. (2022) The pH robustness of bacterial sensing. mBio e0165022.

Feng, H., Lv, Y., Krell, T., Fu, R., Liu, Y., Xu, Z., Du, W., Shen, Q., Zhang, N. Zhang, R. (2022) Signal binding at both modules of its dCache sensor domain enables the McpA chemoreceptor of Bacillus velezensis to sense different ligands. Proc. Natl. Acad. Sci USA 119:e2201747119

Gumerov, V.M., Andrianova, E.P., Matilla, M.A., Page, K.M., Monteagudo-Cascales, E. Dolphin, A.C., Krell, T. Zhulin, I.B. (2022) Amino acid sensor from bacteria to humans. Proc. Natl. Acad. Sci. USA 119: e2110415119.

Matilla, M.A., Velando, F., Tajuelo, A., Martín-Mora, D., Xu, W., Sourjik, V., Gavira, J.A., Krell, T. (2022) Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter acetylcholine. mBio: e0345821

Matilla, M.A., Velando, F., Martín-Mora, D., Monteagudo-Cascales, E., Krell, T. (2022) A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators. FEMS Microbiol Rev. 10.1093/femsre/fuab043

Matilla, M.A., Martín-Mora, D., Gavira, J.A., Krell, T. (2021)  Pseudomonas aeruginosa as a model to study chemosensory pathway signaling. Microbiol. Mol. Biol. Rev. 85(1):e00151-20

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

Cerna-Vargas, J.P., Santamaría-Hernando, S., Matilla, M.A., Rodríguez-Herva, J.J., Daddaoua, A., Rodríguez-Palenzuela, P., Krell, T. López-Solanilla, E. (2019)  Chemoperception of specific amino acids controls phytopathogenicity in P. syringae pv. Tomato.  mBio 10:e01868-19.

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. 46:11229-11238 46:11229-11238

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 regulatorScience Signaling 9(409):ra1.

García Fontana, C., Corral-Lugo, A., Krell, T. (2014) Specificity of the CheR2 Methyltransferase in Pseudomonas aeruginosa is Directed by C-Terminal Pentapeptides in ChemoreceptorsScience Signaling 7 (320) ra34.

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 sitesProc. Acad. Natl. Sci. USA. 109, 18926-18931.

Matilla, M.A., Krell, T. (2018) The effect of bacterial chemotaxis on host infection and pathogenicity. FEMS Microbiol Rev. 42:10.1093/femsre/fux052.

Ortega, Á., Zhulin, I.B., Krell, T. (2017) Sensory Repertoire of Bacterial Chemoreceptors. Microbiol. Mol. Biol. Rev. 81: e00033-17.