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Article ; Online: Efficient markerless integration of genes in the chromosome of probiotic E. coli Nissle 1917 by bacterial conjugation.

Seco, Elena M / Fernández, Luis Ángel

2021 Volume 15, Issue 5, Page(s) 1374–1391

Abstract: The probiotic strain Escherichia coli Nissle 1917 (EcN) is a common bacterial chassis in synthetic biology developments for therapeutic applications given its long track record of safe administration in humans. Chromosomal integration of the genes of ... ...

Abstract	The probiotic strain Escherichia coli Nissle 1917 (EcN) is a common bacterial chassis in synthetic biology developments for therapeutic applications given its long track record of safe administration in humans. Chromosomal integration of the genes of interest (GOIs) in the engineered bacterium offers significant advantages in genetic stability and to control gene dose, but common methodologies relying on the transformation of EcN are inefficient. In this work, we implement in EcN the use of bacterial conjugation in combination with markerless genome engineering to efficiently insert multiple GOIs at different loci of EcN chromosome, leaving no antibiotic resistance genes, vector sequences or scars in the modified bacterium. The resolution of cointegrants that leads to markerless insertion of the GOIs requires expression of I-SceI endonuclease and its efficiency is enhanced by λ Red proteins. We show the potential of this strategy by integrating different genes encoding fluorescent and bioluminescent reporters (i.e. GFP, mKate2, luxCDABE) both individually and sequentially. We also demonstrate its application for gene deletions in EcN (ΔflhDC) and to replace the endogenous regulation of chromosomal locus (i.e. flhDC) by heterologous regulatory elements (e.g. tetR-Ptet) in order to have an ectopic control of gene expression in EcN with an external inducer to alter bacterial behaviour (e.g. flagellar motility). Whole-genome sequencing confirmed the introduction of the designed modifications without off-target alterations in the genome. This straightforward approach accelerates the generation of multiple modifications in EcN chromosome for the generation of living bacterial therapeutics.
MeSH term(s)	Chromosomes ; Conjugation, Genetic ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Infections ; Escherichia coli Proteins/metabolism ; Humans ; Probiotics
Chemical Substances	Escherichia coli Proteins
Language	English
Publishing date	2021-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.13967
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Article ; Online: Intento incompleto de alfabeto para un congreso de la semFYC.

Guillén, María Del Mar / Oliva-Fanlo, Bernardino / Muñoz Seco, Elena

Atencion primaria

2021 Volume 54, Issue 1, Page(s) 102249

Title translation	Incomplete attempt at an alphabet for a semFYC congress.
MeSH term(s)	Community Medicine ; Family Practice ; Humans ; Societies, Medical ; Spain
Language	Spanish
Publishing date	2021-11-25
Publishing country	Spain
Document type	Editorial
ZDB-ID	1200787-0
ISSN	1578-1275 ; 0212-6567
ISSN (online)	1578-1275
ISSN	0212-6567
DOI	10.1016/j.aprim.2021.102249
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Article ; Online: Bacillus subtilis DNA polymerases, PolC and DnaE, are required for both leading and lagging strand synthesis in SPP1 origin-dependent DNA replication.

Seco, Elena M / Ayora, Silvia

Nucleic acids research

2017 Volume 45, Issue 14, Page(s) 8302–8313

Abstract: Firmicutes have two distinct replicative DNA polymerases, the PolC leading strand polymerase, and PolC and DnaE synthesizing the lagging strand. We have reconstituted in vitro Bacillus subtilis bacteriophage SPP1 θ-type DNA replication, which initiates ... ...

Abstract	Firmicutes have two distinct replicative DNA polymerases, the PolC leading strand polymerase, and PolC and DnaE synthesizing the lagging strand. We have reconstituted in vitro Bacillus subtilis bacteriophage SPP1 θ-type DNA replication, which initiates unidirectionally at oriL. With this system we show that DnaE is not only restricted to lagging strand synthesis as previously suggested. DnaG primase and DnaE polymerase are required for initiation of DNA replication on both strands. DnaE and DnaG synthesize in concert a hybrid RNA/DNA 'initiation primer' on both leading and lagging strands at the SPP1 oriL region, as it does the eukaryotic Pol α complex. DnaE, as a RNA-primed DNA polymerase, extends this initial primer in a reaction modulated by DnaG and one single-strand binding protein (SSB, SsbA or G36P), and hands off the initiation primer to PolC, a DNA-primed DNA polymerase. Then, PolC, stimulated by DnaG and the SSBs, performs the bulk of DNA chain elongation at both leading and lagging strands. Overall, these modulations by the SSBs and DnaG may contribute to the mechanism of polymerase switch at Firmicutes replisomes.
MeSH term(s)	Bacillus subtilis/metabolism ; Bacillus subtilis/virology ; Bacterial Proteins/metabolism ; Bacteriophages/genetics ; Bacteriophages/metabolism ; Base Sequence ; DNA Polymerase III/metabolism ; DNA Primase/metabolism ; DNA Replication ; DNA, Single-Stranded/metabolism ; DNA, Viral/genetics ; DNA, Viral/metabolism ; DNA-Binding Proteins/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Electrophoresis, Agar Gel ; Protein Binding ; Replication Origin/genetics
Chemical Substances	Bacterial Proteins ; DNA, Single-Stranded ; DNA, Viral ; DNA-Binding Proteins ; DNA Polymerase III (EC 2.7.7.-) ; DNA Primase (EC 2.7.7.-) ; DNA polymerase III, alpha subunit (EC 2.7.7.-) ; PolC protein, bacteria (EC 2.7.7.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2017-08-21
Publishing country	England
Document type	Journal Article
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkx493
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Article ; Online: Bacillus subtilis RarA modulates replication restart.

Carrasco, Begoña / Seco, Elena M / López-Sanz, María / Alonso, Juan C / Ayora, Silvia

Nucleic acids research

2018 Volume 46, Issue 14, Page(s) 7206–7220

Abstract: The ubiquitous RarA/Mgs1/WRNIP protein plays a crucial, but poorly understood role in genome maintenance. We show that Bacillus subtilis RarA, in the apo form, preferentially binds single-stranded (ss) over double-stranded (ds) DNA. SsbA bound to ssDNA ... ...

Abstract	The ubiquitous RarA/Mgs1/WRNIP protein plays a crucial, but poorly understood role in genome maintenance. We show that Bacillus subtilis RarA, in the apo form, preferentially binds single-stranded (ss) over double-stranded (ds) DNA. SsbA bound to ssDNA loads RarA, and for such recruitment the amphipathic C-terminal domain of SsbA is required. RarA is a DNA-dependent ATPase strongly stimulated by ssDNA-dsDNA junctions and SsbA, or by dsDNA ends. RarA, which may interact with PriA, does not stimulate PriA DNA unwinding. In a reconstituted PriA-dependent DNA replication system, RarA inhibited initiation, but not chain elongation. The RarA effect was not observed in the absence of SsbA, or when the host-encoded preprimosome and the DNA helicase are replaced by proteins from the SPP1 phage with similar function. We propose that RarA assembles at blocked forks to maintain genome integrity. Through its interaction with SsbA and with a preprimosomal component, RarA might impede the assembly of the replicative helicase, to prevent that recombination intermediates contribute to pathological DNA replication restart.
MeSH term(s)	Adenosine Triphosphatases/chemistry ; Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA Replication/genetics ; DNA, Bacterial/chemistry ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/genetics ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Genome, Bacterial/genetics ; Models, Molecular ; Nucleic Acid Conformation ; Protein Binding ; Protein Domains ; Substrate Specificity
Chemical Substances	Bacterial Proteins ; DNA, Bacterial ; DNA, Single-Stranded ; DNA-Binding Proteins ; DNA (9007-49-2) ; Adenosine Triphosphatases (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2018-06-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gky541
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Article ; Online: Recomendaciones sobre el estilo de vida. Actualización PAPPS 2022.

Córdoba García, Rodrigo / Camarelles Guillem, Francisco / Muñoz Seco, Elena / Gómez Puente, Juana M / San José Arango, Joaquín / Ramírez Manent, José Ignacio / Martín Cantera, Carlos / Del Campo Giménez, María / Revenga Frauca, Juan / Egea Ronda, Ana / Cervigón Portaencasa, Raquel / Rodríguez Benito, Laura

Atencion primaria

2022 Volume 54 Suppl 1, Page(s) 102442

Abstract: We present the recommendations of the Preventive Activities and Health Promotion Programme (PAPPS) of the semFYC (Spanish Society of Family and Community Medicine) to promote healthy lifestyles using intervention methodology, and preventive actions ... ...

Title translation	PAPPS expert group: Lifestyle recommendations.
Abstract	We present the recommendations of the Preventive Activities and Health Promotion Programme (PAPPS) of the semFYC (Spanish Society of Family and Community Medicine) to promote healthy lifestyles using intervention methodology, and preventive actions against tobacco and alcohol use, healthy eating, physical activity in leisure time, prevention of traffic accidents, and child restraint systems. The recommendations have been updated, and new aspects highlighted, such as the definition of low-risk alcohol consumption, and the references have been updated. For the main recommendations, we include specific tables showing the quality of the evidence and the strength of the recommendation.
MeSH term(s)	Child ; Humans ; Life Style ; Health Promotion ; Community Medicine ; Healthy Lifestyle ; Exercise
Language	Spanish
Publishing date	2022-11-23
Publishing country	Spain
Document type	English Abstract ; Journal Article
ZDB-ID	1200787-0
ISSN	1578-1275 ; 0212-6567
ISSN (online)	1578-1275
ISSN	0212-6567
DOI	10.1016/j.aprim.2022.102442
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Article ; Online: Grupo de expertos del PAPPS. Recomendaciones sobre el estilo de vida.

Córdoba García, Rodrigo / Camarelles Guillem, Francisco / Muñoz Seco, Elena / Gómez Puente, Juana M / San José Arango, Joaquín / Ramírez Manent, Jose Ignacio / Martín Cantera, Carlos / Del Campo Giménez, María / Revenga Frauca, Juan

Atencion primaria

2021 Volume 52 Suppl 2, Page(s) 32–43

Abstract: Primary and secondary health determinants explain a large part of the morbidity and mortality observed in primary care. The recommendations of the Program of Preventive Activities and Health Promotion (PAPPS) of the semFyC are presented, for the ... ...

Title translation	PAPPS expert group. Lifestyle recommendations.
Abstract	Primary and secondary health determinants explain a large part of the morbidity and mortality observed in primary care. The recommendations of the Program of Preventive Activities and Health Promotion (PAPPS) of the semFyC are presented, for the promotion of a healthy lifestyle through intervention methodology and preventive actions in tobacco consumption, alcohol consumption, healthy eating, physical activity in free time and prevention of traffic accidents and child restraint systems. The most common clinical prevention guidelines are outlined. The recommendations are updated, new aspects are pointed out, such as the definition of low-risk alcohol consumption, and the bibliography is updated. For the main recommendations, specific tables are included that show the quality of the evidence and the strength of the recommendation.
MeSH term(s)	Child ; Exercise ; Health Promotion ; Healthy Lifestyle ; Humans ; Life Style ; Primary Health Care
Language	Spanish
Publishing date	2021-01-02
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1200787-0
ISSN	1578-1275 ; 0212-6567
ISSN (online)	1578-1275
ISSN	0212-6567
DOI	10.1016/j.aprim.2020.07.004
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Article ; Online: New Rimocidin/CE-108 Derivatives Obtained by a Crotonyl-CoA Carboxylase/Reductase Gene Disruption in Streptomyces diastaticus var. 108: Substrates for the Polyene Carboxamide Synthase PcsA.

Escudero, Leticia / Al-Refai, Mahmoud / Nieto, Cristina / Laatsch, Hartmut / Malpartida, Francisco / Seco, Elena M

PloS one

2015 Volume 10, Issue 8, Page(s) e0135891

Abstract: The rimJ gene, which codes for a crotonyl-CoA carboxylase/reductase, lies within the biosynthetic gene cluster for two polyketides belonging to the polyene macrolide group (CE-108 and rimocidin) produced by Streptomyces diastaticus var. 108. Disruption ... ...

Abstract	The rimJ gene, which codes for a crotonyl-CoA carboxylase/reductase, lies within the biosynthetic gene cluster for two polyketides belonging to the polyene macrolide group (CE-108 and rimocidin) produced by Streptomyces diastaticus var. 108. Disruption of rimJ by insertional inactivation gave rise to a recombinant strain overproducing new polyene derivatives besides the parental CE-108 (2a) and rimocidin (4a). The structure elucidation of one of them, CE-108D (3a), confirmed the incorporation of an alternative extender unit for elongation step 13. Other compounds were also overproduced in the fermentation broth of rimJ disruptant. The new compounds are in vivo substrates for the previously described polyene carboxamide synthase PcsA. The rimJ disruptant strain, constitutively expressing the pcsA gene, allowed the overproduction of CE-108E (3b), the corresponding carboxamide derivative of CE-108D (3a), with improved pharmacological properties.
MeSH term(s)	Amide Synthases/metabolism ; Carbon-Carbon Ligases/genetics ; Carbon-Carbon Ligases/metabolism ; Genetic Engineering ; Macrolides/chemistry ; Macrolides/metabolism ; Monosaccharides/chemistry ; Monosaccharides/metabolism ; Polyenes/chemistry ; Polyenes/metabolism ; Streptomyces/enzymology ; Streptomyces/genetics ; Streptomyces/metabolism ; Substrate Specificity
Chemical Substances	CE-108 ; Macrolides ; Monosaccharides ; Polyenes ; rimocidin (72LLC1Q06O) ; Amide Synthases (EC 6.3.1.-) ; Carbon-Carbon Ligases (EC 6.4.-)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0135891
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Article ; Online: Clinical association between Kikuchi׳s disease and systemic lupus erythematosus: A systematic literature review.

Sopeña, Bernardo / Rivera, Alberto / Chamorro, Antonio / Freire, Mayka / Alende, Vanessa / Seco, Elena / González-Gay, Miguel A / González-Quintela, Arturo

Seminars in arthritis and rheumatism

2017 Volume 47, Issue 1, Page(s) 46–52

Abstract: Objective: To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE).: Methods: We ... ...

Abstract	Objective: To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE). Methods: We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients. Results: The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio = 5.0); mean age at diagnosis was 34 years (range: 14-56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis. Conclusions: While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE.
Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	120247-9
ISSN	1532-866X ; 0049-0172
ISSN (online)	1532-866X
ISSN	0049-0172
DOI	10.1016/j.semarthrit.2017.01.011
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Article ; Online: Bacillus subtilis DisA helps to circumvent replicative stress during spore revival.

Raguse, Marina / Torres, Rubén / Seco, Elena M / Gándara, Carolina / Ayora, Silvia / Moeller, Ralf / Alonso, Juan C

DNA repair

2017 Volume 59, Page(s) 57–68

Abstract: The mechanisms that allow to circumvent replicative stress, and to resume DNA synthesis are poorly understood in Bacillus subtilis. To study the role of the diadenylate cyclase DisA and branch migration translocase (BMT) RadA/Sms in restarting a stalled ... ...

Abstract	The mechanisms that allow to circumvent replicative stress, and to resume DNA synthesis are poorly understood in Bacillus subtilis. To study the role of the diadenylate cyclase DisA and branch migration translocase (BMT) RadA/Sms in restarting a stalled replication fork, we nicked and broke the circular chromosome of an inert mature haploid spore, damaged the bases, and measured survival of reviving spores. During undisturbed ripening, nicks and breaks should be repaired by pathways that do not invoke long-range end resection or genetic exchange by homologous recombination, after which DNA replication might be initiated. We found that DNA damage reduced the viability of spores that lacked DisA, BMT (RadA/Sms, RuvAB or RecG), the Holliday junction resolvase RecU, or the translesion synthesis DNA polymerases (PolY1 or PolY2). DisA and RadA/Sms, in concert with RuvAB, RecG, RecU, PolY1 or PolY2, are needed to bypass replication-blocking lesions. DisA, which binds to stalled or reversed forks, did not apparently affect initiation of PriA-dependent DNA replication in vitro. We propose that DisA is necessary to coordinate responses to replicative stress; it could help to circumvent damaged template bases that otherwise impede fork progression.
Language	English
Publishing date	2017-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2071608-4
ISSN	1568-7856 ; 1568-7864
ISSN (online)	1568-7856
ISSN	1568-7864
DOI	10.1016/j.dnarep.2017.09.006
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Article ; Online: The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution.

Mosquera Orgueira, Adrián / Antelo Rodríguez, Beatriz / Alonso Vence, Natalia / Díaz Arias, José Ángel / Díaz Varela, Nicolás / Pérez Encinas, Manuel Mateo / Allegue Toscano, Catarina / Goiricelaya Seco, Elena María / Carracedo Álvarez, Ángel / Bello López, José Luis

BMC cancer

2019 Volume 19, Issue 1, Page(s) 515

Abstract: Background: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad ... ...

Abstract	Background: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth. Methods: Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated. Results: Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNα13 and Nitric oxide was associated with overall survival. Conclusion: Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings.
MeSH term(s)	Biomarkers, Tumor/genetics ; Female ; GTP-Binding Protein alpha Subunits, G12-G13/genetics ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; MAP Kinase Kinase Kinase 4/genetics ; Male ; Phosphoprotein Phosphatases/genetics ; Survival Analysis ; Whole Exome Sequencing/methods
Chemical Substances	Biomarkers, Tumor ; GNA13 protein, human ; MAP Kinase Kinase Kinase 4 (EC 2.7.11.25) ; MAP3K4 protein, human (EC 2.7.11.25) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; protein phosphatase 4 (EC 3.1.3.16) ; GTP-Binding Protein alpha Subunits, G12-G13 (EC 3.6.5.1)
Language	English
Publishing date	2019-05-29
Publishing country	England
Document type	Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-019-5628-y
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