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Antibiotic resistance

Specialized Group:

Beatriz Rojo-Bezares and Yolanda Sáenz Domínguez

Molecular Microbiology Area, La Rioja Biomedical Research Center (CIBIR), Logroño (La Rioja)

ysaenz@riojasalud.es

Group photo. From left to right: Beatriz Rojo-Bezares, Paula Toledano, José Manuel Azcona-Gutiérrez, María López, Gabriela Chichón and Yolanda Sáenz.

Bacterial infections remain a major problem in human and animal health; as well as bacterial contamination in food or in the environment. This problem is accentuated by the alarming increase and spread of bacteria resistant to antibiotics, and by the scarcity of therapeutic alternatives available to combat them. From the Biomedical Research Center of La Rioja (CIBIR), the Molecular Microbiology group joins the global effort to fight the problem of bacterial resistance to antibiotics.

Our group, led by Dr. Yolanda Sáenz and made up of chemists, biologists, biochemists, pharmacists and doctors, began in 2008 with the main purpose of characterizing the mechanisms that bacteria develop to resist the action of antibiotics, to increase their virulence or to ward off environmental pressures or the host's immune system. Likewise, this research helps us identify new therapeutic targets and discover new antimicrobial compounds that combat these pathogens.

With an interdisciplinary approach using techniques of microbiology, molecular and cellular biology, biochemistry, massive sequencing or transcriptomics, we intend to answer questions such as:

Why do the available antibiotics not have activity against pathogenic bacteria? Is there the same pathogenic behavior among a bacterial species of clinical origin as of animal, food or environmental origin? Why is a bacterial species imposed in infections of certain patients, What Pseudomonas aeruginosa In patients with cystic fibrosis? Can we relate the knowledge of the genome of a bacterium with its capacity for infection or persistence? Are there new targets or therapeutic technologies that facilitate the control and eradication of different pathogenic bacteria?

We collaborate with different hospitals, research and technology centers both in personnel training and in research work. In our laboratory, each year we have 3-5 students on national and international internships or stays. In addition, we give courses and seminars to researchers, specialists and students and we provide support and service to companies.

 

Lines of investigation

Pseudomonas aeruginosa: origin, resistance, virulence and pathogenesis

The main line of research focuses on the species P. aeruginosa, one of the most responsible for hospital infections and the cause of serious complications in chronic respiratory diseases (cystic fibrosis, COPD). This pathogen is an important health problem, given its high levels of resistance to antibiotics and virulence; as well as its great ubiquity and difficulty of eradication. Therefore, this problem is not limited to the hospital environment, but requires an analysis in different ecological niches.

Over the past 10 years, our group has built a wide collection of P. aeruginosa from clinical and non-clinical samples (individuals and healthy animals, food and the environment) in which the following is investigated: i) the levels of resistance to various antibiotics and the molecular mechanisms involved, ii) the presence of mobilizable genetic elements, iii) the biological factors involved in the pathogenesis (secretion systems, pigments, elastases, motility, biofilm, etc.), iv) bacterial toxicity and virulence using cell or animal models, v) complete genome by massive sequencing, iv) new therapeutic targets.

from clinical and non-clinical samples (individuals and healthy animals, food and the environment) in which the following is investigated: i) the levels of resistance to various antibiotics and the molecular mechanisms involved, ii) the presence of mobilizable genetic elements, iii) the biological factors involved in the pathogenesis (secretion systems, pigments, elastases, motility, biofilm, etc.), iv) bacterial toxicity and virulence using cell or animal models, v) complete genome by massive sequencing, iv) new therapeutic targets. P. aeruginosa in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis.

 

in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis.

in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. Streptococcus agalactiae in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. bovis and in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. among others. In the absence of preventive measures, In the absence of preventive measures, In the absence of preventive measures, In the absence of preventive measures,, In the absence of preventive measures,In the absence of preventive measures,

The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis.

The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis. In the absence of preventive measures, The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis. The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis.The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis. in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis. bovis The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis. The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis.The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis. In the absence of preventive measures, The objectives of our research include analyzing the mechanisms of resistance to antimicrobials and heavy metals, mechanisms of virulence and molecular typing of isolates, studying the mobile genetic elements involved in the dissemination and transfer of resistance and pathogenesis.

 

Bacterial genomics

In the last two years, we have included genomic tools in our research, based on massive sequencing, not only for the study of P. aeruginosa and in fecal samples from healthy individuals, the first description of strains carrying the ExlA cytotoxin from animal and environmental samples, the detection of new integrons carrying carbapenemase-encoding genes and the characterization of high-risk clones in clinical and non-clinical strains . Likewise, with the collaboration of the group of Dr. A. Prince of Columbia University (New York, USA), we discovered that the accumulation of succinate favors the growth and adaptation of this bacterium to the lungs of patients with cystic fibrosis., but also to characterize enterobacteria carrying carbapenemases. With these tools, we determine resistome, viruloma, mobilizable genetic elements, pathogenicity islands, etc. that allow us to find out the structures involved in the spread of resistance to carbapenems; as well as the clonal and evolutionary relationship in said bacterial genera.

 

New therapies with antimicrobial or antibiofilm activity against pathogenic bacteria

Available antibiotics are less and less effective, so there is an urgent need to apply new antimicrobials to prevent the growth and spread of pathogenic bacteria of clinical, animal, food and environmental importance. Cold atmospheric plasma is a technique capable of inhibiting microbial growth, and since it does not involve extreme conditions, its use has been suggested to decontaminate surfaces without affecting their structure.

From the Molecular Microbiology group we propose to search for new antimicrobial alternatives, which include new chemical compounds, nanoparticles, peptides or bacteriocins, natural products obtained from bacteria, fungi, plants, animals and algae; as well as the use of cold atmospheric plasma as an antimicrobial and antibiofilm technique.

 

Finally, we are introducing nanotechnology procedures in the laboratory for the multivalent immobilization of the aforementioned compounds on nanoparticles of a different chemical nature, with the ultimate goal of substantially increasing their activity, thus reducing the necessary doses.

Riquelme SA , Lozano C , Moustafa AM , Liimatta K , Tomlinson KL , Britto C , Khanal S , Gill SK , Narechania A , Azcona-Gutierrez JM , DiMango E , Saenz Y , Planet P , Prince A. (2019). CFTR-PTEN-dependent mitochondrial metabolic dysfunction promotes Pseudomonas aeruginosa airway infection. Sci Transl Med 11(499). eaav4634.

Lozano C , Azcona-Gutierrez JM , Van Bambeke F , Saenz Y . (2018). Great phenotypic and genetic variation among successive chronic Pseudomonas aeruginosa from a cystic fibrosis patient. PLoS One 13(9):e0204167.

Ruiz-Roldán L, Bellés A, Bueno J, Azcona-Gutiérrez JM, Rojo-Bezares B, Torres C, Castillo FJ, Sáenz Y, Seral C. Terceti MS, Vences A, Matanza XM, Dalsgaard I, Pedersen K, and Osorio CR. Pseudomonas aeruginosa isolates from Spanish children: occurrence in faecal samples, antimicrobial resistance, virulence, and molecular typing. Biomed Res Int 2018:8060178.

Rojo-Bezares B, Estepa V, Cebollada R, de Toro M, Somalo S, Seral C, Castillo FJ, Torres C, Sáenz Y. (2014). Carbapenem-resistant Pseudomonas aeruginosa strains from a Spanish hospital: characterization of metallo-beta-lactamases, porin OprD and integrons. Int J Med Microbiol 304(3-4): 405-14.

Estepa V, Rojo-Bezares B, Torres C, Sáenz Y. (2014). Faecal carriage of Pseudomonas aeruginosa in healthy humans: antimicrobial susceptibility and global genetic lineages. FEMS Microbiol Ecol 89(1): 15-9.

Estepa V, Rojo-Bezares B, Torres C, Saenz Y. (2015). Genetic lineages and antimicrobial resistance in Pseudomonas spp. isolates recovered from food samples. Foodborne Pathog Dis 12(6): 486-91.

Rojo-Bezares B, Steppe V, de Bull M, Undabeitia E, Olarte I, Torres C, Saenz Y. (2011). A novel class 1 integron array carrying blaVIM-2 genes and a new insertion sequence in a Pseudomonas aeruginosa strain isolated from a Spanish hospital. J Med Microbiol 60(Pt 7): 1053-4.

Rojo-Bezares B, Azcona-Gutiérrez JM, Martin C, Jareño MS, Torres C, Sáenz Y. major virulence factors Damselysin, Phobalysin P and Phobalysin C. Front Microbiol, 8:582. Streptococcus agalactiae from pregnant women: antibiotic and heavy-metal resistance mechanisms and molecular typing. Epidemiol Infect 144(15): 3205-14.

Porres-Osante N, Azcona-Gutiérrez JM, Rojo-Bezares B, Undabeitia E, Torres C, Sáenz Y. Porres-Osante N, Azcona-Gutiérrez JM, Rojo-Bezares B, Undabeitia E, Torres C, Sáenz Y. Escherichia coli Porres-Osante N, Azcona-Gutiérrez JM, Rojo-Bezares B, Undabeitia E, Torres C, Sáenz Y.

Porres-Osante N, Azcona-Gutiérrez JM, Rojo-Bezares B, Undabeitia E, Torres C, Sáenz Y. Porres-Osante N, Azcona-Gutiérrez JM, Rojo-Bezares B, Undabeitia E, Torres C, Sáenz Y.

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Porres-Osante N, Azcona-Gutiérrez JM, Rojo-Bezares B, Undabeitia E, Torres C, Sáenz Y.