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.
Ruiz-Cruz, S., Moreno-Blanco, A., Espinosa, M. and Bravo, A. . DNA-binding properties of MafR, a global regulator of Enterococcus faecalis. FEBS Lett. 592 (8): 1412-1425.
Lorenzo-Díaz, F., Fernández-López, C., Guillén-Guío, B., Bravo, A. and Espinosa, M. . Relaxase MobM induces a molecular switch at its cognate origin of transfer. Front. Mol. Biosci. 5: 17. doi: 10.3389/fmolb.2018.00017.
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. . 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 . 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
Lorenzo-Diaz F, Fernández-Lopez C, Douarre PE, Baez-Ortega A, Flores C, Glaser P, Espinosa M . Streptococcal Group B integrative and mobilizable Element IMESagrpsI encodes a functional relaxase involved in its transfer. Open Biology 6: 160084. doi: 10.1098/rsob.160084
Solano-Collado V, Hüttener M, Espinosa M, Juárez A, Bravo A . MgaSpn and H-NS: two unrelated global regulators with similar DNA-binding properties. Front. Mol. Biosci. 3:60. doi: 10.3389/fmolb.2016.00060.
Ruiz-Cruz S, Espinosa M, Goldmann O, Bravo A . 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 . 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 . 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 . The pneumococcal MgaSpn virulence transcriptional regulator generates multimeric complexes on linear double-stranded DNA. Nucleic Acids Res 41: 6975–6991.
Chan WT, Espinosa M . The Streptococcus pneumoniae pezAT toxin-antitoxin system reduces β-lactam resistance and genetic competence. Front. Microbiol. 7:1322. doi: 10.3389/fmicb.2016.01322.
Fernández-López C, Bravo A, Ruiz-Cruz, S, Solano-Collado V, Garsin DA, Lorenzo-Díaz F, Espinosa M . Mobilizable Rolling-Circle Replicating Plasmids from Gram-Positive Bacteria: A Low-Cost Conjugative Transfer. Microbiol Spectrum. 2 (5): PLAS-0008-2013; doi:10.1128/microbiolspec.PLAS-0008-2013.
Solano-Collado V, Espinosa M, Bravo A . Activator role of the pneumococcal Mga-like virulence transcriptional regulator. J. Bacteriol. 194: 4197-4207.
2006-2009. BFU2006-08487/BMC. Ministry of Education and Science. P.I.: A. Bravo.
2006-2010. S-BIO-0260. COMBACT. Autonomous Community of Madrid. Coordinator: M. Vicente.
2009-2012. EU-CP223111 (CAREPNEUMO). European Union. Coordinator: S. Chhatwal.
2008-2011. BFU2008-00179-E/BMC. Ministry of Science and Innovation. Spanish Network of Extrachromosomal Elements (REDEEX). Coordinator: M. Espinosa.
2008-2015. CSD2008-00013 (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.
2017-2019. BIO2016-76412-C2-2-R. Ministry of Economy and Competitiveness. P.I.: A. Bravo.
C. Nieto, P. Acebo, P. Fernández de Palencia, M.A. Corrales, M. Espinosa y P. López. “Procedure for the construction and preparation of fluorescent Gram-positive bacteria”. 2000. Patent PCT Nº PCT/ES00/00305. CSIC.
S. Ruiz-Cruz, V. Solano-Collado, M. Espinosa and A. Bravo. "Novel plasmid-based genetic tools for Gram-positive bacteria". 2010. Reference ES1641.715. Application P201030841. CSIC
Inmaculada Moreno Córdoba. Doctorate Thesis, 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.
María Virtudes Solano Collado. Doctorate Thesis, European Mention (25/04/2014). Molecular characterization of the MgaSpn transcriptional regulator of Streptococcus pneumoniae. Complutense University of Madrid, Faculty of Biological Sciences. Supervisor: A. Bravo.
Cristina Fernández López. Doctorate Thesis, European Mention (10/12/2015). Conjugative relaxases of the MOBV family. Complutense University of Madrid, Faculty of Chemical Sciences. Supervisors: L. F. Lorenzo and M. Espinosa.
Sofía Isabel Ruiz Cruz. Doctorate Thesis, European Mention (17/12/2015). Molecular characterization of an Enterococcus faecalis transcriptional regulator of the Mga/AtxA family. Complutense University of Madrid, Faculty of Biological Sciences. Supervisor: A. Bravo
M. Espinosa has been a member of the Selection Committee of the Young Investigators Programme of EMBO (2007-2010).
M. Espinosa has been a member of the Selection Committee of the EMBO Long Term Fellowships (2008-2012).
M. Espinosa has been elected President of the International Society of Plasmid Biology (2012-2014).
A. Bravo has been a member of the Scientific Committee in the 12th European Meeting on the Molecular Biology of the Pneumococcus. 2015, Oxford, UK.
Web of the special issue (co-edited by M. Espinosa) in Frontiers Molecular Biosciences: http://journal.frontiersin.org/researchtopic/4283/modulating-prokaryotic-lifestyle-by-dna-binding-proteins
Web of the International Society of Plasmid Biology: http://www.ispb.org/