Research Divisions

Molecular Microbiology

Group LeaderLocation and ContactMembersLines of ResearchNotable PublicationsProjectsPhD ThesesPatents and TrademarksNews
Dr Miguel Ángel Álvarez
Dr Miguel Ángel Álvarez

Miguel Ángel Álvarez González

Miguel A. Alvarez obtained his Bachelor’s degree (1987) and PhD in Biology (1991) at the Universitdad de Oviedo. He completed several doctoral fellowships at the John Innes Institute in Norwich (England) and a postdoctoral fellowship as Assistant Lecturer at the ETH Zürich (Switzerland). In 1995, motivated by both the scientific excellence and personal qualities of Professor Juan Evaristo Suárez, as well as the importance of the dairy sector in Asturias, he joined Professor Evaristo Suárez’s research group on a Ministry of Education and Science reincorporation contract, beginning his research on lactic acid bacteria (LAB) and their bacteriophages. In 1999, he obtained the post of CSIC Research Scientist, joining the Instituto de Productos Lácteos de Asturias (IPLA-CSIC), where he established the Molecular Microbiology research group, which he continues to lead today. In 2009, he was promoted to Senior Research Scientist. Throughout his time at IPLA-CSIC, he has continued to work on LAB and their phages, and has initiated new lines of research, a highlight of which has been the exploration of biogenic amines in foodstuffs, as the group has become an international leader in this field. He has also pioneered bacterial genome editing, having developed a system of integration/purification that enables the expression of genes integrated into the genome of LAB while maintaining their food-grade status. Dr Alvarez has been principal investigator on five EU projects, several Spanish National and Regional RDI Plan projects, and projects funded by the private sector. He has published over 100 international articles, most of which appeared in first-quartile (JCR-ranked) journals, has supervised six PhD theses and is the inventor of 12 patents, three of which have been licensed to companies.

Instituto de Productos Lácteos de Asturias (IPLA-CSIC)

Paseo Rio Linares s/n

33300 Villaviciosa (Asturias), Spain.

NamePositionOrganisation
Miguel Ángel Álvarez GonzálezPrincipal InvestigatorCSIC
Baltasar Mayo PérezSenior Research ScientistCSIC
María Fernández GarcíaResearch ScientistCSIC
Víctor Ladero LosadaResearch ScientistCSIC
Beatriz del Rio LagarPostdoctoral ResearcherCSIC
Alfonso Hernández MagadánPostdoctoral ResearcherCSIC
Ana Belén Flórez GarcíaPostdoctoral ResearcherCSIC
Lucía Vázquez IglesiasPhD Researcher on the FPI (Research Staff Training) programmeCSIC
María Agustina SarquisPhD StudentCSIC
Lorena Sampedro AresTechnical and Professional OfficerCSIC

 

Biogenic Amines

Biogenic amines (BA) are low-molecular-weight organic nitrogen compounds which are synthesised through the enzymatic decarboxylation of certain amino acids and perform a very wide range of biological functions in practically all living organisms. However, consumption of contaminated food with a high concentration of BA causes health problems that can become severe. The most toxic BAs are histamine and tyramine, which mainly accumulate in fish and fermented foodstuffs, due to the presence of microorganisms with the relevant amino-acid decarboxylase activity. Our group has made a very significant contribution to the advances in knowledge over the past decade about BAs and the microorganisms responsible for their accumulation in cheese: one of the foodstuffs which can develop the highest concentrations of BAs. However, this is a complex problem which has not yet been solved. Our objective in this field is to conduct in-depth research into the biological mechanisms that lead to BA synthesis. This enables us to rationally design strategies to avoid their accumulation in fermented foodstuffs, focusing particularly on cheese.

Human Gastrointestinal Microbiology and the Selection of Probiotics

We have characterised the microbiology of several sections of the gastrointestinal tract (GIT) using culture dependent and independent techniques , our main objective being to identify microbial types that may be used in food systems – specifically, in dairy products – as biotechnological agents or probiotic microorganisms. Our most important achievements include the development of extensive collections of lactic acid bacteria (LAB) and bifidobacteria which originate in the GIT and have beneficial properties that make them suitable for use as new or more robust probiotics. In the immediate future, our core objectives are: (i) to contribute to knowledge about the health benefits of isoflavones through research into their metabolism by intestinal populations of bacteria (ii) to identify and select strains of bacteria that create desirable transformations in isoflavones (including equol production), for use in functional foodstuffs. After ingestion, isoflavones are activated by components of the microbiota which have yet to be adequately characterised. Identifying and characterising these microorganisms and their activities will enable them to be put to use in functional foodstuffs.

Resistance to Antibiotics in the Food Chain

Antibiotic-resistant food bacteria can act as reservoirs of resistance genes which may be transferred to pathogenic microorganisms during food production or after consumption, during intestinal transit. This line of research is an essential step in characterising ferments and selecting probiotics, enabling us to detect strains that are resistant to several antibiotics and analyse their molecular bases. Our current objectives are: To analyse the resistome of cheese for a representative group of antibiotics (TC, ERY, AP, VM . Etc.), quantify the various resistance genes in artisan and industrially-produced cheeses, and identify the microbial groups and species involved in this resistance, assessing the risk of their transfer to pathogens in dairy products.

Probiotics as Live Vectors for the Production of Therapeutic Molecules in Mucus

Lactobacilli are non-pathogenic LAB which have been given QPS (Qualified Presumption of Safety) status by the EFSA, meaning that they are considered safe for human consumption. Some strains are well-known probiotics with high levels of consumer acceptance, and can survive or even colonise the mucus in the gastrointestinal tract and vagina. We have therefore suggested that lactobacilli are ideal for use as live vectors for the production of therapeutic agents in mucus. The cost-effectiveness of this strategy is worth highlighting, as the bacteria are easy to cultivate and the costs of production and purification of the therapeutic agent are saved. The strategy also avoids the problem of degradation, which is particularly serious in the gastrointestinal tract. Another factor to consider is that these bacteria can withstand lyophilisation, avoiding the need for a refrigeration chain.

The food-grade genetic tools developed by our group place us at the forefront of this field. In the near future, our work will focus on constructing lactobacilli which produce various types of proteins with activity against certain multidrug-resistant pathogens in mucus, as an alternative to treatment with antibiotics.

Isolating and Characterising Bacteriophages to Develop Biotechnological and Biocontrol Tools for Food Spoilage Bacteria and Multidrug-resistant Pathogenic Bacteria

Our group has a long history of research on the viruses that infect bacteria: known as bacteriophages or simply phages. In addition to the great theoretical interest of studying host-parasite interactions, investigating the molecular biology of the phages that infect LAB enables us to develop new food-grade genetic tools. We are also interested in the use of bacteriophages and their lysines (the enzymes that break the cell wall, enabling virions to be released at the end of the lytic cycle) as highly-specific weapons for the biocontrol of spoilage microorganisms in food, and also as an alternative to antibiotics for treating multidrug-resistant pathogenic bacteria.

  • Daniel M. Linares, Beatriz del Rio, B. Redruello, V. Ladero, M. C. Martin, M. Fernandez, P. Ruas-Madiedo and Miguel A. Alvarez “Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine” Food Chemistry 197: 658-663 (2016)

Impact factor: 4.529 Quartile: 1

  • Maria Diaz, B. del Río, E. Sanchez-Llana, V. Ladero, B. Redruello, M. Fernández, M. C. Martin and Miguel A. Alvarez “Histamine-producing Lactobacillus parabuchneri strains isolated from grated cheese can form biofilms on stainless steel” Food Microbiology 59: 85-91 (2016)

Impact factor: 4.090 Quartile: 1

  • Beatriz del Rio, D. Linares, V. Ladero, B. Redruello, M. Fernández, M. C. Martin and Miguel A. Alvarez “Putrescine biosynthesis in Lactococcus lactis is transcriptionally activated at acidic pH and counteracts acidification of the cytosol” International Journal of Food Microbiology 236: 83-89 (2016)

Impact factor: 3.451 Quartile: 1

  • Marta Perez, V. Ladero, B. Redruello, B. del Rio, L. Fernandez, J.M. Rodriguez, M. C. Martin, M. Fernández, and Miguel A. Alvarez “Mastitis modifies the biogenic amines profile in human milk, with significant changes in the presence of histamine, putrescine and spermine” PLOS One 11(9): e0162426 (2016)

Impact factor: 2.766 Quartile: 1

  • Guadamuro, L., Jiménez-Girón, A., Delgado, S., Flórez, A. B., Martín-Álvarez, P. J., Suárez, A., Bartolomé, B., Moreno-Arribas, V., and Mayo, B. “Profiling of phenolic metabolites in faeces from equol-producing and non-producing menopausal women after long-term isoflavone supplementation” Journal of Agriculture and Food Chemistry 64: 210-216 (2016)

Impact factor: 3.412 Quartile: 1

  • Flórez, A. B., I. Campedelli, S. Delgado, Á. Alegría, E. Salvetti, G. E. Felis, B. Mayo, and S. Torriani. “Antibiotic susceptibility profiles of dairy Leuconostoc, analysis of the genetic basis of atypical resistances and transfer of genes in vitro and in a food matrix” PLoS One 11: e0145203 (2016)

Impact factor: 2.766 Quartile: 1

  • Flórez, A. B., Sierra, M., Ruas-Madiedo, P., and Mayo, B. “Susceptibility of lactic acid bacteria, bifidobacteria and bacteria of intestinal origin to antitumor compounds used in breast and lung cancer” International Journal of Antimicrobial Agents 48: 547-55. (2016)

Impact factor: 4.307 Quartile: 1

  • Rychlik, T., Szwengiel, S., Bednarek, M., Arcuri, E., Montet, D., Mayo, B., Nowak, J., and Czarnecki, Z. “Application of the PCR-DGGE technique to the fungal community of traditional Wielkopolska fried ripened curd cheese to determine its PGI authenticity” Food Control 73: 1074-1081 (2016)

Impact factor: 3.667 Quartile: 1

  • Delgado, S., Flórez, A. B., Guadamuro, L., and Mayo, B. “Genetic and biochemical characterization of an oligo-α-1,6-glucosidase from Lactobacillus plantarumInternational Journal of Food Microbiology 246: 32-39 (2016)

Impact factor: 3.451 Quartile: 1

  • Flórez, A. B., Vázquez, L., Mayo, B. “A functional metagenomic analysis of tetracycline resistance in cheese bactéria” Frontiers in Microbiology 8: 907 (2016)

Impact factor: 4.076 Quartile: 1

  • Vázquez, L., Guadamuro, L., Giganto, F., Mayo, B., Flórez, A. B. “Development and application of a real-time quantitative PCR method for detecting and quantifying equol-producing bacteria in faecal samples and cultures” Frontiers in Microbiology 8: 1155 (2016)

Impact factor: 4.076 Quartile: 1

  • Guadamuro, L., Flórez, A. B., Vázquez, L., Mayo, B. “Characterization of Bifidobacterium pseudocatenulatum β-glucosidases involved in the release of aglycones from isoflavone-glycosides” Food Research International 100: 522-528 (2016)

Impact factor: 3.520 Quartile: 1

  • Flórez, A. B., Mayo, B. “Antibiotic resistance-susceptibility profiles of wild Streptococcus thermophilus strains isolated from raw milk and genome analysis of the genetic basis of adquired resistances” Frontiers in Microbiology 8: 2608 (2016)

Impact factor: 4.076 Quartile: 1

  • Beatriz del Rio, Begoña Redruello, D. M. Linares, V. Ladero, M. Fernández, M. C. Martin, P. Ruas-Madiedo and Miguel A. Alvarez “The dietary biogenic amines tyramine and histamine show synergistic toxicity towards intestinal cells in culture” Food Chemistry 218: 249-255 (2017)

Impact factor: 4.946 Quartile: 1

  • Begoña Redruello, V. Ladero, B. del Rio, M. Fernández, M. C. Martin and Miguel A. Alvarez “A UHPLC method for the simultaneous analysis of biogenic amines, amino acids and ammonium ions in beer” Food Chemistry 217: 117-124 (2017)

Impact factor: 4.946 Quartile: 1

  • Marta Perez, V. Ladero, B. del Rio, B. Redruello, A. de Jong, O. Kuipers, J. Kok, M. C. Martin, M. Fernandez, Miguel A. Alvarez “The relationship among tyrosine decarboxylase and agmatine deiminase pathways in Enterococcus faecalis” Frontiers in Microbiology 8: 2107 (2017)

Impact factor: 4.076 Quartile: 1

  • Beatriz del Rio, P. Alvarez-Sieiro, B. Redruello, M. C. Martin, M. Fernandez, V. Ladero and Miguel A. Alvarez “Lactobacillus rossiae strain isolated from sourdough produces putrescine from arginine” Scientific Reports 8: 3989 (2018)

Impact factor: 4.122 Quartile: 1

  • Beatriz del Rio, B. Redruello, D.M. Linares, V. Ladero, P. Ruas-Madiedo, M. Fernández, M. C. Martin and Miguel A. Alvarez “Spermine and spermidine are cytotoxic towards intestinal cell cultures, but are they a health hazard at concentrations found in foods?” Food Chemistry 269: 321-326 (2018)

Impact factor: 4.946 Quartile: 1

  • Beatriz del Rio, B. Redruello, V. Ladero, S. Cal, A. Obaya and Miguel A. Alvarez “An altered gene expression profile in tyramine-exposed intestinal cell cultures supports the genotoxicity of this biogenic amine at dietary concentrations” Scientific Reports 8: 17038 (2018)

Impact factor: 4.122 Quartile: 1

  • Beatriz del Rio, B. Redruello, D. M. Linares, V. Ladero, P. Ruas-Madiedo, M. Fernandez, M. C. Martin, and Miguel A. Alvarez “The biogenic amines putrescine and cadaverine show in vitro cytotoxicity at concentrations that can be found in foods” Scientific Reports (En prensa)

Impact factor: 4.122 Quartile: 1

Principal InvestigatorTitleFunding BodyReference NoDurationAmount
Baltasar Mayo PérezFunctional characterisation of autochthonous strains of Streptococcus thermophilus, isolated in traditional Spanish cheeses, and their environmentINIA (National Institute for Agricultural and Food Research and Technology)RM2011-00005-00-00January 2012 – December 2014€55,876.80
Baltasar Mayo PérezMetabolism of soy isoflavones by gut microbiota during menopause: identification, characterisation and selection of probiotics for the formulation of soy-derived functional dairy productsMINECOAGL2011-24300-ALIJanuary 2012 – December 2014€157,300
Baltasar Mayo PérezIdentification and selection of equol-producing and/or 5-hydroxy-equol-producing intestinal bacteria for use in functional foodMINECOAGL-2014-57820-RJanuary 2015 – December 2017€175,450
María Fernández and María Cruz MartínUnderstanding the accumulation of biogenic amines in cheese: from toxicology to accumulationMINECOAGL2013-45431-RJanuary 2015 – December 2017€170,000
Miguel Ángel ÁlvarezMolecular Biology Research GroupFICYT (Foundation for the Promotion of Applied Scientific Research and Technology in Asturias), Gobierno Principado de AsturiasGRUPIN14-1371/1/2014 – 31/12/2017€156,600
Miguel Ángel ÁlvarezBiogenic amines: toxicity, factors involved in their biosynthesis and new strategies to prevent their accumulation in fermented foodstuffsMINECOAGL2016-78708-R30/12/2016 – 29/12/2020€223,850
Miguel Ángel ÁlvarezPromotion of local Mediterranean fermented foodstuffs through improved knowledge and management of microbial resourcesEuropean Union (ERA-NET ARIMNet2)/ INIAPROMEFOODS-ARIMNet201/10/2017 – 30/09/2020€42,500
Miguel Ángel ÁlvarezMolecular Biology Research GroupFICYT, Gobierno Principado de AsturiasGRUPIN 201801/01/2018 – 31/12/2020€145,200

 

SupervisorsTitlePhD StudentOrganisationYearHonours
Víctor LaderoMiguel A. ÁlvarezBiosynthesis of biogenic amines in lactic acid bacteria: genetic regulation and physiological and technological implicationsMarina M. Calles EnriquesUniversidad de Oviedo2014
María Fernández Miguel A. ÁlvarezBiosynthesis of biogenic amines in human breast milk bacteria: possible physiological implicationsMarta Pérez GarcíaUniversidad de Oviedo2015
María C. Martín Miguel A. ÁlvarezIdentification and characterisation of the bacteria responsible for the accumulation of histamine in cheeseMaría Díaz GarcíaUniversidad de Oviedo2016
Baltasar Mayo Pérez Susana Delgado PalacioSoya isoflavones and microbial populations in the intestine: identification and characterisation of microorganisms involved in their metabolismLucía Guadamuro GarcíaUniversidad de Oviedo2017International honours

 

InventorsTitleRegistration Number
Baltasar MayoSusana DelgadoA probiotic strain of Lactobacillus reuteri with anti-Helicobacter activity, probiotic or biotherapeutic products containing it and the use thereofPCT/ES2014/070666
Patricia Alvarez-SieiroM. Cruz Martin

Begoña Redruello

Víctor Ladero

María Fernández

Miguel A Alvarez

A new strain of Lactobacillus casei with the ability to degrade the immunotoxic peptide from glutenPCT PD10109PC00