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Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC) and Institute of Livestock Development and Animal Health (INDEGSAL)

Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC)
e Instituto de Desarrollo Ganadero y Sanidad Animal (INDEGSAL)
Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC)

Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC)

Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC)
Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC) Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC)

Department of Molecular Biology, Institute of Molecular Biology, Genomics and Proteomics (INBIOMIC)

LINES OF INTEREST AND RESEARCH ACTIVITY

The research group in the microbiology area of ​​the University of León, led by Prof. Luis M. Mateos, has extensive experience in the study of certain Redox systems present in actinobacteria. His research work has allowed the discovery of mycorredoxins (Mrx), essential proteins in the intracellular Redox control of these bacteria and whose mechanism of action is linked to the antioxidant molecule mycothiol (MSH). The MSH/Mrx system serves to preserve the reduced intracellular state, essential for the proper functioning of most protein systems in actinobacteria.

In addition to the aforementioned system, the group of Prof. Mateos has focused its studies on other essential proteins for the control of the Redox state. Among them, the work carried out in collaboration with the group of Dr. Messens of the "Vrije Universiteit Brussel" in Belgium stands out. In this way, the essential role played by the OxyR protein in the rapid response of the bacteria against oxidative stress was demonstrated, using the catalase protein (KatA) as a regulator, which is activated in the presence of hydrogen peroxide (hydrogen peroxide, H2O2) ( Pedre et al., 2019).

Recently, Prof. Mateos began to consider whether these systems based on MSH/Mrx could also be a survival system for intracellular pathogens during infectious processes. Bacteria of the phylum Actinobacteria that behave as intracellular pathogens (Mycobacterium tuberculosis O Rhodococcus equi among others) present important Redox control systems, for which they have up to three possible mycorredoxins in their genome, among other components. In addition, representatives of this group also use the Redox system thioredoxin/thioredoxin reductase (Trx/TrxR), whose presence is ubiquitous in practically all the organisms studied. Finally, these bacteria present a new system of extracellular thioredoxins (Etrx) that seem to be anchored to the cytoplasmic membrane and oriented towards the extracellular space.

The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.

As a model of infection, the group has focused on The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria., which is an intracellular pathogen that affects foals and humans, among many other hosts. That is why this pathogen is important in human health, but it also generates significant economic losses in the field of equine farming, associated with the death of different farm animals. This sector is valued at 5,000 million euros in Spain according to the Ministry of Agriculture, Fisheries and Food. This line of research was based on the study of the importance of Redox control systems during the infection of The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.. Prof. Mateos' group developed genetically engineered mutants in which the coding genes for each of the three mycorredoxins that have been described to date in the genome of . Prof. Mateos' group developed genetically engineered mutants in which the coding genes for each of the three mycorredoxins that have been described to date in the genome of . Prof. Mateos' group developed genetically engineered mutants in which the coding genes for each of the three mycorredoxins that have been described to date in the genome of

. Prof. Mateos' group developed genetically engineered mutants in which the coding genes for each of the three mycorredoxins that have been described to date in the genome of The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.. Prof. Mateos' group developed genetically engineered mutants in which the coding genes for each of the three mycorredoxins that have been described to date in the genome of

Overall, the sensitivity of all the mutant strains described above against oxidizing compounds, such as hydrogen peroxide or sodium hypochlorite, was analyzed. Subsequently, in vitro macrophage infection studies were carried out, which were developed in collaboration with researchers at the University of Roehampton (London). These tests made it possible to demonstrate that both the absence of mycorredoxins and of the thioredoxin Etrx3 caused a marked attenuation of The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.Overall, the sensitivity of all the mutant strains described above against oxidizing compounds, such as hydrogen peroxide or sodium hypochlorite, was analyzed. Subsequently, in vitro macrophage infection studies were carried out, which were developed in collaboration with researchers at the University of Roehampton (London). These tests made it possible to demonstrate that both the absence of mycorredoxins and of the thioredoxin Etrx3 caused a marked attenuation of

Next, the team studied in more detail the oxidation-reduction process during intracellular infection caused by The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.. To do this, they used the roGFP2 oxidative stress sensor (Gutscher et al., 2008), so that by fusing it to each of the mycorredoxins, it allowed us to evaluate the Redox state of the mycothiol at each moment of infection. In this way, it was possible to identify the specific points of the infection in which a greater oxidative stress was produced. On the other hand, it was also shown that the role of a mycorredoxin could be replaced by any of the other two present in the genome, since complementation with only one of these three proteins served to restore the wild-type phenotype in the triple mutant. from The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.. In addition, a certain sequential role in the function of each of these proteins could be observed during the infection process.

. In addition, a certain sequential role in the function of each of these proteins could be observed during the infection process. The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria.. In addition, a certain sequential role in the function of each of these proteins could be observed during the infection process. The hypothesis from which Prof. Mateos' group started was that these bacteria, being intracellular pathogens, would be subject to an intense state of oxidative stress, upon being recognized and phagocytosed by host macrophages. These macrophages constitute the first line of defense in the lung and activate a series of proteins whose main function is to generate oxidative stress in the phagocytosed bacteria to destroy it. However, many intracellular pathogens are capable of resisting this oxidative stress and colonizing the intracellular environment, which is why Prof. Mateos' group focused on the study of Redox control systems in actinobacteria. (Mourenza et al. 2020b), at a time when more and more strains of this pathogen that are resistant to antibiotics are being isolated. Based on the above, we believe that these studies may serve as a starting point for the search for new treatments against other intracellular pathogens multiresistant to antimicrobials whose incidence and mortality are increasing dramatically, such as Mycobacterium tuberculosis.

CONTRIBUTION AND SELECTED PUBLICATIONS

  1. (Mourenza et al. 2020b), at a time when more and more strains of this pathogen that are resistant to antibiotics are being isolated. Based on the above, we believe that these studies may serve as a starting point for the search for new treatments against other intracellular pathogens multiresistant to antimicrobials whose incidence and mortality are increasing dramatically, such as (Mourenza et al. 2020b), at a time when more and more strains of this pathogen that are resistant to antibiotics are being isolated. Based on the above, we believe that these studies may serve as a starting point for the search for new treatments against other intracellular pathogens multiresistant to antimicrobials whose incidence and mortality are increasing dramatically, such as
  2. (Mourenza et al. 2020b), at a time when more and more strains of this pathogen that are resistant to antibiotics are being isolated. Based on the above, we believe that these studies may serve as a starting point for the search for new treatments against other intracellular pathogens multiresistant to antimicrobials whose incidence and mortality are increasing dramatically, such as (2019) Mycoredoxins are required for redox homeostasis and intracellular survival in the actinobacterial pathogen Rhodococcus equi. Antioxidants 8: 558.
  3. (2019) Mycoredoxins are required for redox homeostasis and intracellular survival in the actinobacterial pathogen Rhodococcus equi. Antioxidants 8: 558. (2019) Mycoredoxins are required for redox homeostasis and intracellular survival in the actinobacterial pathogen Rhodococcus equi. Antioxidants 8: 558.
  4. (2019) Mycoredoxins are required for redox homeostasis and intracellular survival in the actinobacterial pathogen Rhodococcus equi. Antioxidants 8: 558. (2019) Mycoredoxins are required for redox homeostasis and intracellular survival in the actinobacterial pathogen Rhodococcus equi. Antioxidants 8: 558.
  5. (2019) Mycoredoxins are required for redox homeostasis and intracellular survival in the actinobacterial pathogen Rhodococcus equi. Antioxidants 8: 558.. (2018) Structural snapshots of OxyR reveal the peroxidatic mechanism of H2O2 sensing. Proc Nat Acad Sci USA 115: E11623–E11632.
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