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Identification of therapeutic targets and development of alternative strategies for the treatment and prevention of bacterial infections

Specialized Group:

Jordi Barbéa, Montserrat Llagosteraa, Susana Campoya, Maria Pilar Cortésa, Jesus Arandaa and Ivan Erillb

aDepartment of Genetics and Microbiology, Faculty of Biosciences, Bellaterra Campus, Autonomous University of Barcelona and Department of Biological Sciences, bUniversity of Maryland, Baltimore County, Baltimore, MD, United States

Jordi.Barbe@uab.cat; Susana.Campoy@uab.cat

Group photo. From left to right, top: Marc Gaona, Jordi Corral, M. Pilar Cortés, Ruth Ricart, Miquel Sánchez-Osuna, Ivan Erill, Joan Ruiz, Jesús Aranda, Montserrat Llagostera and Jordi Barbé. Bottom: Susana Escribano, Elisabeth Frutos, Susana Campoy, Julia López and Jennifer Otero

The selection and dispersion of multiresistant bacteria resulting from the abusive use of antibiotics in their different fields of application, has caused a decrease in the effectiveness of the available antimicrobial compounds. This represents one of the greatest challenges of our society and of public health worldwide, since it not only entails a high health cost, but also, year after year, the number of deaths due to these recalcitrant pathogens is constantly increasing.

Understanding the molecular mechanisms that govern the behavior of bacterial pathogens is essential for the development of therapies that act differently from known antimicrobial systems and allow the prevention and treatment of infectious diseases.

In this scenario, the research lines of our group try to delve into the identification of new therapeutic targets and the development of alternative strategies that allow increasing the efficiency and the variety of tools focused on the treatment and prevention of infections caused by bacteria resistant to the antibiotics.

Since the beginning of our journey, in 1985, the mechanisms associated with DNA repair, and specifically those that refer to the SOS system, a gene response that is activated in the presence of DNA lesions, have been one of the bases in our research. Our studies have made it possible to define the genetic network of this system and characterize its regulation in a multitude of microorganisms, tracing the possible evolution of this response throughout the Bacteria Domain (Erill et al., 2007). Furthermore, we have linked the implication of the SOS system with the ability to spread antibiotic resistance and islands of pathogenicity and other virulence factors (Guerin et al., 2009). More recently, our studies have shown that the positive regulator of the SOS response, RecA, is directly associated with chemotaxis and some surface movements, such as swarming O twitching in Salmonella enterica o en Acinetobacter baumannii, respectively (Irazoki et al., 2016). Studies on the motility of A. baumannii (Pérez-Varela et al., 2017), have led to a new research project in which we have been able to show how transporters belonging to practically all the families of flow pumps described, in addition to their role in resistance, are involved in motility and virulence. of this microorganism (Pérez-Varela et al.The selection and dispersion of multiresistant bacteria resulting from the abusive use of antibiotics in their different fields of application, has caused a decrease in the effectiveness of the available antimicrobial compounds. This represents one of the greatest challenges of our society and of public health worldwide, since it not only entails a high health cost, but also, year after year, the number of deaths due to these recalcitrant pathogens is constantly increasing.

Another important line of work in our group has been the study of divalent cation uptake systems, essential trace elements for most living organisms. Within the host, the available concentration of these is extraordinarily low, so that pathogenic bacteria have developed high-affinity uptake systems that allow them to survive in these environments. These mechanisms are exposed on the surface of the pathogen and are usually highly immunogenic, making them perfect candidates for the development of immunotherapy strategies. Our group has studied the collection systems and their control mechanisms in S. enterica, Pasteurella multocida, Streptococcus suis, Haemophilus parasuisS. enterica, Pasteurella multocida, Streptococcus suis, Haemophilus parasuis et al.S. enterica, Pasteurella multocida, Streptococcus suis, Haemophilus parasuis et al.S. enterica, Pasteurella multocida, Streptococcus suis, Haemophilus parasuisEnterococcus spp, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.) of hospital origin, and that make up a group of bacterial species for which the World Health Organization determined as a priority the search for new strategies for their treatment given their high degree of multidrug resistance. The main objective of this project is the development of broad spectrum active and passive immunotherapy mechanisms based on the conservation of these high affinity uptake systems between different isolates and species.

A third treatment alternative in which our group has been dedicated for more than ten years is the biotechnological application of bacteriophages using as a model S. enterica. As a result of this research, we have developed a cocktail of different bacteriophages that has been successfully applied as oral therapy in broilers experimentally infected with S. enterica in conditions that mimic those of a commercial farm (Colom et al., 2015; Colom et al., 2017), and also in the treatment of experimentally contaminated food (Spricigo et al., 2013). Thanks to the collaboration with the NanoChemistry and Supramolecular Materials group led by Dr. Daniel Maspoch of the Catalan Institute of Nanotechnology (ICN2), we have developed different strategies for encapsulating bacteriophages with different biocompatible materials, which give them stability by increasing their residence time. and significantly prolonging its therapeutic effect after its administration in oral therapy (Colom et al., 2015; Colom et al., 2017). Continuing along this line, our current and future interest lies in determining and characterizing the mechanisms of resistance to bacteriophages in different fields of application and also in further analyzing their genomes in order to determine new functions that help guarantee the safety of the future phage-based products. Related to this, we are involved in a H2020 Fast Track to Innovation project for the development of a biocidal commercial product and a food additive based on bacteriophages for the control of S. enterica.

Throughout our history, our interest in transferring to society all our knowledge acquired in basic research. For this reason, technology transfer is also an axis that articulates this group reflected in the obtaining of various patents related to divalent cation and bacteriophage capture systems, the latter of international concession and licensed for its exploitation.

In addition, we also try to promote the relationship with the productive sector of our society by offering services, establishing agreements and / or contracts with companies, in order, based on our experience, to stimulate the transfer of technology and knowledge.

 

Bibliography

, 2017). Continuing along this line, our current and future interest lies in determining and characterizing the mechanisms of resistance to bacteriophages in different fields of application and also in further analyzing their genomes in order to determine new functions that help guarantee the safety of the future phage-based products. Related to this, we are involved in a H2020 Fast Track to Innovation project for the development of a biocidal commercial product and a food additive based on bacteriophages for the control of (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of Streptococcus suis. (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of

(2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of Sci Rep (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of

(2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of Salmonella spp. Appl Environ Microbiol (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of

(2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of FEMS Microbiol Rev (2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of

(2012) Inactivation of the gene encoding zinc-binding lipoprotein 103 impairs the infectivity of et al. (2009) The SOS response controls integron recombination. (2009) The SOS response controls integron recombination. (2009) The SOS response controls integron recombination.

(2009) The SOS response controls integron recombination. (2009) The SOS response controls integron recombination. Salmonella enterica. PLoS One (2009) The SOS response controls integron recombination.

(2009) The SOS response controls integron recombination. (2009) The SOS response controls integron recombination. Acinetobacter baumannii. Infect Immun (2009) The SOS response controls integron recombination.

(2009) The SOS response controls integron recombination. (2009) The SOS response controls integron recombination. Acinetobacter baumannii (2009) The SOS response controls integron recombination. Antimicrob Agents Chemother (2009) The SOS response controls integron recombination.

(2009) The SOS response controls integron recombination. (2013) Use of a bacteriophage cocktail to control Salmonella (2013) Use of a bacteriophage cocktail to control (2013) Use of a bacteriophage cocktail to control (2013) Use of a bacteriophage cocktail to control

(2013) Use of a bacteriophage cocktail to control (2013) Use of a bacteriophage cocktail to control Salmonella enterica (2013) Use of a bacteriophage cocktail to control in vivo and in vitro. PLoS One (2013) Use of a bacteriophage cocktail to control

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(2013) Use of a bacteriophage cocktail to control