Group Leader/s
Head of lab
intro
The bottom-line of our work is to understand the mechanisms involved in gene regulation and gene transfer in Gram-positive bacteria. From a holistic point of view, these mechanisms contribute to evolutionary processes that increase the adaptation of bacteria to new niches. Known examples are provided by opportunistic Gram-positive bacteria that turn from a commensally lifestyle to an infective situation. In our case, the bacteria under study are Streptococcus pneumoniae (the pneumococcus) and Enterococcus faecalis. The former colonizes the nasopharynx of up to 80% of ‘healthy’ individuals. However, after invasion of new niches, like the lungs, pneumococcus becomes virulent, leading to a high toll in human lives, especially elderly population and children below 5 years. E. faecalis is a ‘respected’ member of the human gut microbiome that can become pathogenic under immunological deprivation. The infectious processes caused by both bacteria involve genetic switches that lead from activation to repression (and vice versa) of a number of operons. One of our main goals is to study basic components of these genetic switches. Further, the mobilome of these bacteria contributes to the acquisition of novel traits, such as antibiotic resistances, that facilitate the successful adaptation to environmental challenges. Finally, participation of toxin-antitoxin operons in biofilm formation or in the uptake of free DNA from the fellow bacteria also contributes to the colonization of new niches.
Selected Publications
Moreno-Blanco A, Solano-Collado V, Ortuno-Camuñas A, Espinosa M, Ruiz-Cruz S, Bravo A [2022]. PclR is a transcriptional activator of the gene that encodes the pneumococcal collagen-like protein PclA. Sci. Rep. 12:11827. doi: 10.1038/s41598-022-15758-7
Yeo CC, Espinosa M, Venkova T [2022]. Editorial: Prokaryotic Communications, Volume II: From Macromolecular Interdomain to Intercellular Talks (Recognition) and Beyond. Front. Mol. Biosci. 9:910673. doi: 10.3389/fmolb.2022.910673
Schleif R, Espinosa M [2022]. Where to From Here?. Front. Mol. Biosci. 9:848444. doi: 10.3389/fmolb.2022.848444
Garcillán-Barcia MP, Pluta R, Lorenzo-Díaz F, Bravo A, Espinosa M [2022]. The facts and family secrets of plasmids that replicate via the rolling-circle mechanism. Microbiol. Mol. Biol. Rev. 86:e00222-20. doi: 10.1128/MMBR.00222-20
Solano-Collado V, Ruiz-Cruz S, Lorenzo-Díaz F, Pluta R, Espinosa M, Bravo A [2021]. Recognition of streptococcal promoters by the pneumococcal SigA protein. Front. Mol. Biosci. 8:666504
Li J, Wang J, Ruiz-Cruz S, Espinosa M, Zhang J, Bravo A [2020]. In vitro DNA inversions mediated by the PsrA site-specific tyrosine recombinase of Streptococcus pneumoniae. Front. Mol. Biosci. 7:43
Ruiz-Cruz S, Moreno-Blanco A, Espinosa M, Bravo A [2019]. Transcriptional activation by MafR, a global regulator of Enterococcus faecalis. Sci. Rep. 9: 6146. doi: 10.1038/s41598-019-42484-4
Ruiz-Cruz, S., Moreno-Blanco, A., Espinosa, M. and Bravo, A. [2018]. DNA-binding properties of MafR, a global regulator of Enterococcus faecalis. FEBS Lett. 592 (8): 1412-1425.
Pluta, R. Boer, R.D., Lorenzo-Díaz, F. Russi, S. Gómez, H., Fernández-López, C. Perez-Luque, R., Orozco, M., Espinosa, M. and Coll, M. [2017]. Structural basis of a novel histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance. Proc. Natl. Acad. Sci. USA. 114, E6526–E6535. doi: 0.1073/pnas.1702971114.
F. Lorenzo-Díaz, C. Fernández-López, R. Lurz, A. Bravo and M. Espinosa [2017]. Crosstalk between vertical and horizontal gene transfer: plasmid replication control by a conjugative relaxase. Nucleic Acids Res (2017) 45: 7774-7785. doi: 10.1093/nar/gkx450
Ruiz-Cruz S, Espinosa M, Goldmann O, Bravo A [2016]. Global regulation of gene expression by the MafR protein of Enterococcus faecalis. Front Microbiol 6:1521 (doi: 10.3389/fmicb.2015.01521)
Chan WT, Balsa D, Espinosa M [2015]. One cannot rule them all: Are bacterial toxins-antitoxins druggable? FEMS Microbiol. Rev. 39(4): 522-540 doi: 10.1093/femsre/fuv002.
Scheb-Wetzel M, Rohde M, Bravo A, Goldmann O [2014]. New insights into the antimicrobial effect of mast cells against Enterococcus faecalis. Infect. Immun. 82: 4496-4507 (doi:10.1128/IAI.02114-14)
Solano-Collado V, Lurz R, Espinosa M, Bravo A [2013]. The pneumococcal MgaSpn virulence transcriptional regulator generates multimeric complexes on linear double-stranded DNA. Nucleic Acids Res 41: 6975–6991.
Solano-Collado V, Hüttener M, Espinosa M, Juárez A, Bravo A [2016]. MgaSpn and H-NS: two unrelated global regulators with similar DNA-binding properties. Front. Mol. Biosci. 3:60. doi: 10.3389/fmolb.2016.00060.
Funding
2008-2015. CSD2008-00013 (CONSOLIDER INTERMODS). Ministry of Science and Innovation. Coordinator: M. Espinosa.
2009. CCG08-CSIC/SAL-3694. Autonomous Community of Madrid-CSIC. P.I.: A. Bravo.
2010-2012. BFU2009-11868 (BMC). Ministry of Science and Innovation. P.I.: A. Bravo.
2013-2015. CSIC-PIE-201320E028. P.I.: A. Bravo.
2014-2016. BIO2013-49148-C2-2-R. Ministry of Economy and Competitiveness. P.I.: A. Bravo.
2015-2017. BIO2015-69085-REDC. Ministry of Economy and Competitiveness. Coordinator: A. Juárez.
2017-2020. BIO2016-76412-C2-2-R. Ministry of Economy and Competitiveness. P.I.: A. Bravo.
2020-2023. PID2019-104553RB-C21. Ministry of Science and Innovation. P.I.: A. Bravo.
More info
THESIS
Inmaculada Moreno-Córdoba, European Mention, 2013. Characterization of the toxin-antitoxin system RelBE2 of Streptococcus pneumoniae. Complutense University of Madrid, Faculty of Biological Sciences. Supervisors: C. Nieto and M. Espinosa.
Virtu Solano-Collado, European Mention, 2014. Molecular characterization of the MgaSpn transcriptional regulator of Streptococcus pneumoniae. Complutense University of Madrid, Faculty of Biological Sciences. Supervisor: A. Bravo.
Cris Fernández-López, European Mention, 2015. Conjugative relaxases of the MOBV family. Complutense University of Madrid, Faculty of Chemical Sciences. Supervisors: L. F. Lorenzo and M. Espinosa.
Sofía Ruiz-Cruz, European Mention, 2015. Molecular characterization of an Enterococcus faecalis transcriptional regulator of the Mga/AtxA family. Complutense University of Madrid, Faculty of Biological Sciences. Supervisor: A. Bravo.
Ana Moreno-Blanco, 2020. Characterization of two transcriptional activators: MafR of Enterococcus faecalis and MgaP of Streptococcus pneumoniae. Complutense University of Madrid, Faculty of Biological Sciences. Supervisor: A. Bravo.
OTHER INFORMATION
M. Espinosa: EMBO member since 1996.
M. Espinosa: President of the International Society of Plasmid Biology, 2012-2014. http://www.ispb.org/
A. Bravo: Member of the Scientific Committee in the 12th European Meeting on the Molecular Biology of the Pneumococcus. 2015, Oxford, UK.
M. Espinosa: Co-editor in Frontiers in Microbiology, Section Evolutionary and Genomic Microbiology, Topic Title: “The Good, The Bad and The Ugly: Multiple Roles of Bacteria in Human Life”. 2017-2018. http://journal.frontiersin.org/researchtopic/5409/the-good-the-bad-and-the-ugly-multiple-roles-of-bacteria-in-human-life
M. Espinosa: Co-editor in Frontiers in Molecular Biosciences, Section Molecular Recognition, Topic Title: “Prokaryotic Communications: From Macromolecular Interdomain to Intercellular Talks (Recognition) and Beyond”. 2019-2020.
http://journal.frontiersin.org/researchtopic/4283/modulating-prokaryotic-lifestyle-by-dna-binding-proteins