Dr Fernando Santos Beneit
I studied Biology at University of León (Spain). I spent ten months as a Socrates-Erasmus grant holder at the department of Molecular Cell Physiology of the “Vrije Universiteit” in Amsterdam (Holland), where I worked with the Gram-negative bacterium, Paracoccus denitrificans. I conducted my PhD in molecular biology at University of León, where I was awarded a PhD (cum laude) in 2010, as well as the 2012 University of León Extraordinary Prize for the best thesis in Biology. I have dedicated ten years to studying phosphate regulation in the model actinomycete Streptomyces coelicolor, with particular focus on secondary metabolite regulation and nutrient stress cross-talk. I developed most of my work at the Institute of Biotechnology of León, but I also collaborated with different researches at the department of Molecular Biology in the Faculty of Biology as well as with several biotechnology companies. In 2013, I worked as postdoctoral researcher in the Institute of Biomedicine and Biotechnology of Cantabria, where my role encompassed not only my ongoing research responsibilities, but also a range of economic and administrative duties. Since 2014 I am working as Research Associate in the Center for Bacterial Cell Biology at Newcastle University where I am studying distinct aspects of the streptomycetes biology.
My research focus on three main aspects of the biology of the antibiotic-producers streptomycetes:
- Control of secondary metabolism. Streptomycetes produce over two-thirds of the clinically useful antibiotics of natural origin today. They also produce other bioactive secondary metabolites, such as antifungal compounds, antitumor agents and immuno-suppressants. The growing gap between the increasing frequency of multidrug-resistant bacteria emerging and the decline in development of new antibiotics makes the discovery and development of novel antibacterial agents an important challenge for science. However, most of the secondary metabolites gene clusters are not expressed under laboratory conditions. Therefore, new insights into antibiotic production regulatory mechanisms are of most important for the discovery of new bioactive compounds.
- Glycopeptide resistance regulation in Streptomyces coelicolor. The majority of the existing bacteria have developed some level of resistance to antibiotics and, what it is worse; many important pathogens have become resistant to many, or even all, available antibiotics. The problem of antimicrobial resistance is even more serious by the fact that few new antibiotics have been developed over the last decades; making crucial the development of new strategies to attack bacteria. Glycopeptides, such as vancomycin, are used as last resort antibiotic treatments for many important bacterial infections. The onset of vancomycin resistance since its introduction in clinics was long-delayed (almost 30 years) in comparison to all other antibiotics. For example, only one or two years after the adoption of penicillin in clinics, resistance was reported. Worryingly, vancomycin resistance has spread to important pathogens like for example Enterococcus faecium or Staphylococcus aureus; major hospital-acquired pathogens. Glycopeptide resistance clusters are found both in the glycopeptide-producing actinomycetes (e.g. Amycolatopsis orientalis, Streptomyces toyocaensis) and also in some non-glycopeptide-producing actinomycetes such as Streptomyces coelicolor. This last bacterium offers a safety (no infection risks) and convenient system (many genetic tools have been developed in the last decades) for the in vivo study of important aspects involve in the resistance mechanism.
- Control of cell division. Although several groups have been working on various cell cycle problems in streptomycetes, much less is known about this general area of their biology in comparison with other bacteria like Bacillus subtilis or Escherichia coli. However, Streptomyces biology brings with it a number of very interesting problems that are not addressable in those other organisms, including: (i) cell wall growth at the tips of filaments (involving the DivIVA protein) rather than the more common intercalating, MreB-dependent mode of cylindrical elongation. That makes DivIVA (normally a non-essential protein in most bacteria) essential in Streptomyces; (ii) hyphal branching as a means of increasing the overall growth rate; (iii) it appears that several genes that are essential in many other organisms turn out apparently to be non-essential in S. coelicolor; most notably the central cell division protein, FtsZ; (iv) in spite of having streptomycetes a huge number of cell-wall hydrolytic enzymes and conserved genes of the divisome, cytokinesis and cell separation is a rare event of their cell cycle. Understanding the mechanisms that control the cell division process is not only important for solving questions such as how life evolved, but also for interfering with essential functions in pathogenic bacteria; thereby facilitating the development of antibiotics with novel modes of action.
- TEACHING ACTIVITIES
18/11/2013 – 29/11/2013: Assistant teacher at the University of Cantabria (Spain)
Masters in Molecular Biology and Biomedicine. “Molecular and Cellular Microbiology”.
01/10/2006 – 30/06/2008: Assistant teacher at the University of León (Spain)
BSc subjects: “Microbiology” and “Industrial Microbiology and Biotechnology”.
- SUPERVISION OF GRADUATE STUDENTS
01/02/2015 – 31/07/2015: MRes student co-supervisor
Medical School, Institute for Cell and Molecular Biosciences, Newcastle University (UK).
01/09/2011 – 31/08/2015: PhD student co-supervisor
Institute of Biotechnology of León (INBIOTEC), University of León (Spain).
- Santos-Beneit F, Gu J-Y, Stimming U, Errington J. ylmD and ylmE genes are dispensable for growth, cross-wall formation and sporulation in Streptomyces venezuelae. Heliyon 2017, 3(11), e00459.
- Santos-Beneit F, Roberts DM, Cantlay S, McCormick JR, Errington J. A mechanism for FtsZ-independent proliferation in Streptomyces. Nature Communications 2017, 8, 1378.
- Ordóñez-Robles M, Santos-Beneit F, Rodríguez-García A, Martín JF. Analysis of the Pho regulon in Streptomyces tsukubaensis. Microbiological Research 2017, 205, 80-87.
- Ordonez-Robles M, Santos-Beneit F, Albillos SM, Liras P, Martin JF, Rodriguez-Garcia A. Streptomyces tsukubaensis as a new model for carbon repression: transcriptomic response to tacrolimus repressing carbon sources. Applied Microbiology and Biotechnology 2017, 101(22), 8181-8195.
- Martín JF, Santos-Beneit F, Sola-Landa A, Liras P. Cross-talk of global regulators in Streptomyces. In: de Bruijn,FJ, ed. Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria. New York: Wiley-Blackwell, 2016, pp.257-262.
- Santos-Beneit F. Are antibiotics weapons against neighbouring bacteria?. Research & Reviews: Journal of Microbiology and Biotechnology 2015, 4(3), 40-41.
- Santos-Beneit F. The Pho regulon: a huge regulatory network in bacteria. Frontiers in Microbiology 2015, 6, 13.
- Beites T, Rodríguez-García A, Santos-Beneit F, Moradas-Ferreira P, Aparicio JF, Mendes MV. Genome-wide analysis of the regulation of pimaricin production in Streptomyces natalensis by reactive oxygen species. Applied Microbiology and Biotechnology 2014, 98(5), 2231-2241.
- Santos-Beneit F, Martín JF, Barreiro C. Glycopeptides and bacterial cell walls. In: Tomás G. Villa, Patricia Veiga-Crespo, ed. Antimicrobial Compounds: Current Strategies and New Alternatives. Berlin: Springer, 2014, pp.285-311.
- Santos-Beneit F. Phosphate Regulation in the Antibiotic-Producers Streptomycetes. In: Tewari, R, ed. Microbial Biotechnology. New Delhi: Studium Press LLC, 2014, pp.135-153.
- Santos-Beneit F, Fernández-Martínez LT, Rodríguez-García A, Martín-Martín S, Ordóñez-Robles M, Yagüe P, Manteca A, Martín JF. Transcriptional response to vancomycin in a highly vancomycin-resistant Streptomyces coelicolor mutant. Future Microbiology 2014, 9, 603-622.
- Santos-Beneit F, Rodríguez-García A, Martín JF. Identification of different promoters in the absA1-absA2 two-component system, a negative regulator of antibiotic production in Streptomyces coelicolor. Molecular Genetics and Genomics 2013, 288(1-2), 39-48.
- Santos-Beneit F, Martín JF. Vancomycin resistance in Streptomyces coelicolor is phosphate dependent but it is not mediated by the PhoP regulator. Journal of Global Antimicrobial Resistance 2013, 1(2), 109-113.
- Fernández-Martínez LT, Santos-Beneit F, Martín JF. Is PhoR-PhoP partner fidelity strict? PhoR is required for the activation of the pho regulon in Streptomyces coelicolor?. Molecular Genetics and Genomics 2012, 287(7), 565-573.
- Santos-Beneit F, Rodríguez-García A, Martín JF. Overlapping binding of PhoP and AfsR to the promoter region of glnR in Streptomyces coelicolor. Microbiological Research 2012, 167(9), 532-535.
- Martín JF, Santos-Beneit F, Rodríguez-García A, Sola-Landa A, Smith MC, Ellingsen TE, Nieselt K, Burroughs NJ, Wellington EM. Transcriptomic studies of phosphate control of primary and secondary metabolism in Streptomyces coelicolor. Applied Microbiology and Biotechnology 2012, 95(1), 61-75.
- Santos-Beneit F, Rodríguez-García A, Martín JF. Complex transcriptional control of the antibiotic regulator afsS in Streptomyces: PhoP and AfsR are overlapping, competitive activators. Journal of Bacteriology 2011, 193, 2242-2251.
- Martín JF, Sola-Landa A, Santos-Beneit F, Fernández-Martínez LT, Prieto C, Rodríguez-García A. Cross-talk of global nutritional regulators in the control of primary and secondary metabolism in Streptomyces. Microbial Biotechnology 2011, 4(2), 165-174.
- Martín JF, Sola-Landa A, Santos-Beneit F, Rodríguez-García A. Network mechanisms of phosphate control of primary and secondary metabolism. In: Paul Dyson, ed. Streptomyces: Molecular Biology and Biotechnology. Wymondham: Caister Academic Press, 2011, pp.137-149.
- Santos-Beneit F, Barriuso-Iglesias M, Fernández-Martínez LT, Martínez-Castro M, Sola-Landa A, Rodríguez-García A, Martín JF. The RNA polymerase omega factor RpoZ is regulated by PhoP and has an important role in antibiotic biosynthesis and morphological differentiation in Streptomyces coelicolor. Applied and Environmental Microbiology 2011, 77(21), 7586-7594.
- Santos-Beneit F, Rodríguez-García A, Sola-Landa A, Martín JF. Cross-talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoRP transcription. Mol Microbiol 2009, 72, 53-68.
- Santos-Beneit F, Rodríguez-García A, Apel AK, Martín JF. Phosphate and carbon source regulation of two PhoP-dependent glycerophosphodiester phosphodiesterase genes of Streptomyces coelicolor. Microbiology 2009, 155, 1800-1811.
- Rodríguez-García A, Sola-Landa A, Apel K, Santos-Beneit F, Martín JF. Phosphate control over nitrogen metabolism in Streptomyces coelicolor: direct and indirect negative control of glnR, glnA, glnII and amtB expression by the response regulator PhoP. Nucleic Acids Res 2009, 37, 3230-3242.
- Santos-Beneit F, Rodríguez-García A, Franco-Domínguez E, Martín JF. Phosphate-dependent regulation of the low- and high-affinity transport systems in the model actinomycete Streptomyces coelicolor. Microbiology 2008, 154, 2356-2370.
- Rodríguez-García A, Barreiro C, Santos-Beneit F, Sola-Landa A, Martín JF. Genome-wide transcriptomic and proteomic analysis of the primary response to phosphate limitation in Streptomyces coelicolor M145 and in a DeltaphoP mutant. Proteomics 2007, 7, 2410-2429.