HOST / BACTERIA INTERACTION
At present, my group is focused on understanding the dialogue of beneficial gut bacteria with the host, in particular lactic acid bacteria (LAB), in other words, we are trying to disclose the mechanisms of action of probiotic bacteria. We aim to disclose the molecular mechanisms of anti-inflammatory and anti-apoptotic activity of a variety of bacterial surface proteins strains of the Lactobacillus casei/rhamnosus group and the corresponding receptors in human epithelial cells and animal models. When these proteins were characterized we found they are cell wall bound proteinases (PrtP) or cell wall lysines (p40, p75) but also surprisingly, glycolytic enzymes that reach the external part of the bacteria through unknown processes. Through the collaboration with Dr. M. Carmen Collado, we also study the relationship of gut bacteria with the host from the broader perspective offered by population studies of the gut microbiota by new generation sequencing techniques and transcriptomics of the host. These studies are shedding light on the relationships of gut microbiota with disease and diet in farm rabbits and aquaculture fish (Sparus aurata), and in collaboration with important hospitals we could determine that preterm infants suffering sepsis change the profile of bacterial populations.
PREVIOUS HISTORY, FROM FILAMENTOUS FUNGI TO FOOD BIOTECHNOLOGY:
A continuous roadway with landmarks. My research interest has evolved remarkably since my PhD on “Protoplast fusion of the antibiotic producing filamentous fungus Acremonium chrysogenum” under the supervision of Prof. J.F. Peberdy at the University of Nottingham (U.K.). However, it constitutes a continuous and progressive change that followed some very rational lines. It may not seem evident, but in the years that took to complete my Thesis (1981-85) protoplast fusion was at the forefront of the techniques to achieve recombination in fungi. Genetic manipulation in Biotechnology was an emerging concept and I moved for the first time in 1985 to the IATA (CSIC, Spanish National Research Council) as a postdoc to start cloning cellulolytic enzymes from gram-positive bacteria. Meanwhile, elementary recombinant techniques had been developed in lactic acid bacteria, a group of bacteria that turned out most relevant in Food Science. This was an emerging field pioneered by a few European groups that included the laboratory of Prof. Gerard Venema in Groningen (The Netherlands). In 1989, I obtained one of the early Postdoc European Grants (BAP Program) to develop the first heterologous protein expression system in lactic acid bacteria under the supervision of Dr. Sierd Bron and Dr. Jan Kok, in Prof. Venema’s laboratory. Then, I obtained a permanent position at the IATA in 1990, and two years later, I started developing the germ of the Lactic Acid Bacteria Laboratory when we obtained successively four projects of the European Commission and suitable projects of the Spanish Commission for Science and Technology. This last organization has been financing our research until today. The subjects we developed at this time were related to the selection of starter cultures for cured meat fermented products and their ability to produce acid from added sugars. Without doubt the metabolism of sugars has been the main subject developed during the following years until present. From The Netherlands, I brought a strain of Lactobacillus casei that we used as reference and model for which I assigned the collection number BL23. We could decipher the mechanism of catabolite repression in this microorganism and various mechanisms of regulation of sugar transport (PTS) and utilization genes, like those for lactose, sorbose, mannose, sorbitol and finally, glucose. This work gave rise to several PhD theses and postdoc stages and it was altogether the germ for profound changes and new research lines, like the analysis of arginine deiminase pathway in L. sakei and the complete sequencing of the genome of BL23 where the participation of Dr. M. Zúñiga essential. Cloning and expression vectors were developed that helped to develop L.casei as a vector for the delivery of oral vaccines, enzymes and potential therapeutic proteins. We had developed “Superprobiotics”; however, little was known on the mechanism of action of probiotics, like some strains of Lactobacillus casei/rhamnosus, for which we started exploring this new research topic since 2005, and the years to come.
CERNADA M., E. SERNA, A. MEJÍAS, O. RAMILO, C. BAUERL, M.C. COLLADO, G. PÉREZ-MARTINEZ, M. VENTO. (2014) Genome-wide expression profiles in very low birth-weight infants with neonatal sepsis. Pediatrics 133(5):e1203-11. doi: 10.1542/peds.2013-2552 ISSN: 210-5721
BAUERL, CHRISTINE, MARTA LLOPIS, MARÍA ANTOLÍN, VICENTE MONEDERO, MANUEL ZÚÑIGA, MANUEL MATA, FRANCISCO GUARNER y GASPAR PÉREZ MARTÍNEZ (2013). Lactobacillus casei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa. Genes and Nutrition 2013 Mar;8(2):165-80. doi: 10.1007/s12263-012-0301 DOI: 10.1007/s12263-012-0301-y.ISSN: 1555-8932
VON SCHILLDE, MA ; HORMANNSPERGER, G ; WEIHER, M ; ALPERT, CA ; HAHNE, H ; PEREZ-MARTINEZ, G ; HALLER, D , VAN HUYNEGEM, K, STEIDLER, L, HRNCIR, T, GASPAR PÉREZ-MARTÍNEZ, KUSTER, B, HALLER, D. (2012) Lactocepin Secreted By Lactobacillus Exerts Anti-Inflammatory Effects By Selectively Degrading Proinflammatory Chemokines. CELL-Host & Microbe 11(4): 387–396 (IF = 13,72) 10.1016/j.chom.2012.02.006.ISSN: 1931-3128
ZUÑIGA M, COMAS I, LINAJE R, MONEDERO V, YEBRA MJ, ESTEBAN CD, DEUTSCHER J, PEREZ-MARTINEZ G, GONZALEZ-CANDELAS F. (2005) Horizontal Gene Transfer in the Molecular Evolution of Mannose PTS Transporters. Mol Biol Evol. 22 (8): 1673-1685.
MONEDERO,V., RODRÍGUEZ-DÍAZ, J., VIANA, R., BUESA, J. y PÉREZ-MARTÍNEZ, G.. (2004) Selection of single-chain antibodies against the VP8* subunit of rotavirus VP4 outer capsid protein and their expression in lactic acid bacteria. Appl Environ Microbiol. 2004 Nov;70(11):6936-9.
- Nº Solicitud:PE 05743929.1Título:Producto fermentado sin lactosa a partir de batido de frutos secos no legumbres y/o horchata
- Nº Solicitud:PE 9500269Título:Mutants in Lactobacillus casei deffective in carbon catabolism regulation.