Luis M Mateos

• Professor
• Group Leader at University of Leon

Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and...

Antibiotherapy is the main therapeutic strategy in the fight against bacterial pathogens. However, the misuse of antimicrobials has led to the appearance of antimicrobial-resistant strains. The rate at which we isolate multidrug-resistant bacteria is now much faster than the discovery rate of new antimicrobials. Therefore, the repurposing of approv...

Every year, we face infectious outbreaks produced by harmful microorganisms commonly called superbugs. Often, there is not enough time to find new treatments to cure infected patients. On average, it takes a decade to develop a promising new drug to the point where it can be used on patients! Also, many of the compounds that we identify in the labo...

Staphylococcal infections are a widespread cause of disease in humans. In particular, S. aureus is a major causative agent of infection in clinical medicine. In addition, these bacteria can produce a high number of staphylococcal enterotoxins (SE) that may cause food intoxications. Apart from S. aureus, many coagulase-negative Staphylococcus spp. c...

Rhodococcus equi is an intracellular veterinary pathogen that is becoming resistant to current antibiotherapy. Genes involved in preserving redox homeostasis could be promising targets for the development of novel anti-infectives. Here, we studied the role of an extracellular thioredoxin (Etrx3/REQ_13520) in the resistance to phagocytosis. An etrx3...

The genus Staphylococcus encompasses many species that may be pathogenic to both humans and farm animals. These bacteria have the potential to acquire multiple resistant traits to the antimicrobials currently used in the veterinary or medical settings. These pathogens may commonly cause zoonoses, and the infections they cause are becoming difficult...

Tuberculosis is the leading cause of death, worldwide, due to a bacterial pathogen. This respiratory disease is caused by the intracellular pathogen Mycobacterium tuberculosis and produces 1.5 million deaths every year. The incidence of tuberculosis has decreased during the last decade, but the emergence of MultiDrug-Resistant (MDR-TB) and Extensiv...

Antimicrobial resistance is becoming one of the most important human health issues. Accordingly, the research focused on finding new antibiotherapeutic strategies is again becoming a priority for governments and major funding bodies. The development of treatments based on the generation of oxidative stress with the aim to disrupt the redox defenses...

Rhodococcus equi is a facultative intracellular pathogen that causes infections in foals and many other animals such as pigs, cattle, sheep, and goats. Antibiotic resistance is rapidly rising in horse farms, which makes ineffective current antibiotic treatments based on a combination of macrolides and rifampicin. Therefore, new therapeutic strategi...

Corynebacterium diphtheriae is a human pathogen that causes diphtheria. In response to immune system–induced oxidative stress, C. diphtheriae expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic m...

Rhodococcus equi is a facultative intracellular pathogen that can survive within macrophages of a wide variety of hosts, including immunosuppressed humans. Current antibiotherapy is often ineffective, and novel therapeutic strategies are urgently needed to tackle infections caused by this pathogen. In this study, we identified three mycoredoxin-enc...

During patient colonization, Staphylococcus aureus is able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased...

Host-directed therapeutics are a promising anti-infective strategy against intracellular bacterial pathogens. Repurposing host-targeted drugs approved by the FDA in the US, the MHRA in the UK and/or regulatory equivalents in other countries, is particularly interesting because these drugs are commercially available, safe doses are documented and th...

Hydrogen peroxide (H 2 O 2 ) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward H 2 O 2 . One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces H 2 O 2 . I...

Staphylococcus aureus escapes from immune recognition by invading a wide range of human cells. Once the pathogen becomes intracellular, the most important last resort antibiotics are not effective. Therefore, novel anti-infective therapies against intracellular S. aureus are urgently needed. Here, we have studied the physiological changes induced i...

The Mycobacterium tuberculosis rv2466c gene encodes an oxidoreductase enzyme annotated as DsbA. It has a CPWC active-site motif embedded within its thioredoxin-fold domain and mediates the activation of the prodrug TP053, a thienopyrimidine derivative that kills both replicating and nonreplicating bacilli. However, its mode of action and actual enz...

Arsenic (As) is widespread in the environment and highly toxic. It has been released by volcanic and anthropogenic activities and causes serious health problems worldwide. To survive arsenic-rich environments, soil and saprophytic microorganisms have developed molecular detoxification mechanisms to survive arsenic-rich environments, mainly by the e...

Cobalt is an essential element, but its wide use in industry generates important environmental and biological problems. The present study explores theoretical and empirical models of a green process for cobalt {Co2+} bioaccumulation from aqueous solutions. Two Gram-positive Bacillus subtilis species, strains CECT 4522 and LMM (the latter a former l...

Cysteine glutathione peroxidases (CysGPxs) control oxidative stress levels by reducing hydroperoxides at the expense of cysteine thiol (-SH) oxidation, and the recovery of their peroxidatic activity is generally accomplished by thioredoxin (Trx). Corynebacterium glutamicum mycothiol peroxidase (Mpx) is a member of the CysGPx family. We discovered t...

The use of members from corynebacteria, a Gram-positive group of actinobacteria, for biochemical transformations and/or production of metabolites is well known since long time ago; in fact the microbial production of metabolites such as several essential amino acids and nucleotides are based on members of the coryneform group. However, very little...

Despite current remediation efforts, arsenic contamination in water sources is still a major health problem, highlighting the need for new approaches. In this work, strains of the nonpathogenic and highly arsenic-resistant bacterium Corynebacterium glutamicum were used as inexpensive tools to accumulate inorganic arsenic, either as arsenate (As(V))...

Bacterial cell size and morphology are enormously diverse. The molecular factors of morphogenesis are well understood in certain bacterial models and fairly conserved throughout a broad spectrum of bacterial species, as follows. In most bacteria, the tubulin-like FtsZ protein polymerizes at the mid cell , thereby generating the scaffold of the bact...

The present clinical scenario is one of a growing number of immuno-compromised patients infected with a variety of fungal pathogens. AIDs, tuberculosis, immunosuppressive therapy, cancer chemotherapy or the use of broad-spectrum antibiotics contribute to the boost of such patient category. However, progress in the treatment of fungal infections has...

Bacterial cell size and morphology are enormously diverse. The molecular factors of morphogenesis are well understood in certain bacterial models and fairly conserved throughout a broad spectrum of bacterial species, as follows. In most bacteria, the tubulin-like FtsZ protein polymerizes at the mid cell , thereby generating the scaffold of the bact...

NrdH-redoxins are small reductases with a high amino acid sequence similarity with glutaredoxins and mycoredoxins but with a thioredoxin-like activity. They function as the electron donor for class Ib ribonucleotide reductases, which convert ribonucleotides into deoxyribonucleotides. We solved the x-ray structure of oxidized NrdH-redoxin from Coryn...

To survive hostile conditions, the bacterial pathogen Mycobacterium tuberculosis produces millimolar concentrations of mycothiol as a redox buffer against oxidative stress. The reductases that couple the reducing power of mycothiol to redox active proteins in the cell are not known. We report a novel mycothiol-dependent reductase (mycoredoxin-1) wi...

Environmental context Industrial development has favoured the release of toxic elements to the environment and monitoring and assessment their environmental impact are key points. An important aspect of understanding these concerns is to evaluate how toxic substances interact with microorganisms, which has critical implications in the environment....

Una reciente publicación científica en la prestigiosa revista “Science” abogaba por la aparición de otro tipo de forma de vida (“extraterrestre” se ha dicho) basándose en la aparente abundancia de resultados proporcionados por el descubrimiento de una bacteria que aparentemente había sustituido el fósforo, uno de los elementos esenciales para la vi...

Although bacteria are considered the simplest life forms, we are now slowly unraveling their cellular complexity. Surprisingly, not only do bacterial cells have a cytoskeleton but also the building blocks are not very different from the cytoskeleton that our own cells use to grow and divide. Nonetheless, despite important advances in our understand...

Resistance to arsenite (As(III)) by cells is generally accomplished by arsenite efflux permeases from Acr3 or ArsB unrelated families. We analyzed the function of three Acr3 proteins from Corynebacterium glutamicum, CgAcr3-1, CgAcr3-2, and CgAcr3-3. CgAcr3-1 conferred the highest level of As(III) resistance and accumulation in vivo. CgAcr3-1 was al...

Arsenate reductases (ArsCs) evolved independently as a defence mechanism against toxic arsenate. In the genome of Corynebacterium glutamicum, there are two arsenic resistance operons (ars1 and ars2) and four potential genes coding for arsenate reductases (Cg_ArsC1, Cg_ArsC2, Cg_ArsC1' and Cg_ArsC4). Using knockout mutants, in vitro reconstitution o...

Corynebacteria grow by wall extension at the cell poles, with DivIVA being an essential protein orchestrating cell elongation and morphogenesis. DivIVA is considered a scaffolding protein able to recruit other proteins and enzymes involved in polar peptidoglycan biosynthesis. Partial depletion of DivIVA induced overexpression of cg3264, a previousl...

Homologues to actin are ubiquitous in nature, and actin-based cellular skeletons are crucial for the maintenance of prokaryotic and eukaryotic cellular morphology. Regarding the prokaryotes, MreB actin-homologues sustain the peptidoglycan (PG) synthesis along the lateral cell wall of most rod-shaped bacteria; FtsA actin-homologues are essential for...

A novel method for the retention of arsenate [As(V)] combining time-controlled solid-phase extraction with living bacterial biomass is presented. As(V) retention was carried out by exposing the extractant, consisting of a living double-mutant of Corynebacterium glutamicum strain ArsC1-C2, to the sample for a retention time of 1-7min, before the ars...

Members of the Acr3 family of arsenite permeases confer resistance to trivalent arsenic by extrusion from cells, with members in every phylogenetic domain. In this study bacterial Acr3 homologues from Alkaliphilus metalliredigens and Corynebacterium glutamicum were cloned and expressed in Esch e richia coli. Modification of a single cysteine residu...

Corynebacterium glutamicum is a rod-shaped actinomycete with a distinct model of peptidoglycan synthesis during cell elongation, which takes place at the cell poles and is sustained by the essential protein DivIVA(CG) (C. glutamicum DivIVA). This protein contains a short conserved N-terminal domain and two coiled-coil regions: CC1 and CC2. Domain d...

Corynebacterium glutamicum contains four serine/threonine protein kinases (STPKs) named PknA, PknB, PknG, and PknL. Here we present the first biochemical and comparative analysis of all four C. glutamicum STPKs and investigate their potential role in cell shape control and peptidoglycan synthesis during cell division. In vitro assays demonstrated t...

We identified the first enzymes that use mycothiol and mycoredoxin in a thiol/disulfide redox cascade. The enzymes are two arsenate reductases from Corynebacterium glutamicum (Cg_ArsC1 and Cg_ArsC2), which play a key role in the defense against arsenate. In vivo knockouts showed that the genes for Cg_ArsC1 and Cg_ArsC2 and those of the enzymes of t...

The Mur ligases play an essential role in the biosynthesis of bacterial cell-wall peptidoglycan and thus represent attractive targets for the design of novel antibacterials. These enzymes catalyze the stepwise formation of the peptide moiety of the peptidoglycan disaccharide peptide monomer unit. MurC is responsible of the addition of the first res...

Expression of the genes for resistance to heavy metals and metalloids is transcriptionally regulated by the toxic ions themselves. Members of the ArsR/SmtB family of small metalloregulatory proteins respond to transition metals, heavy metals, and metalloids, including As(III), Sb(III), Cd(II), Pb(II), Zn(II), Co(II), and Ni(II). These homodimeric r...

Corynebacterium glutamicum contains four serine/threonine protein kinases (STPKs) named PknA, PknB, PknG, and PknL. Here we present the first biochemical and comparative analysis of all four C. glutamicum STPKs and investigate their potential role in cell shape control and peptidoglycan synthesis during cell division. In vitro assays demonstrated t...

Bacterial cell growth and cell division are highly complicated and diversified biological processes. In most rod-shaped bacteria, actin-like MreB homologues produce helicoidal structures along the cell that support elongation of the lateral cell wall. An exception to this rule is peptidoglycan synthesis in the rod-shaped actinomycete Corynebacteriu...

The actinomycete Corynebacterium glutamicum grows as rod-shaped cells by zonal peptidoglycan synthesis at the cell poles. In this bacterium, experimental depletion of the polar DivIVA protein (DivIVACg) resulted in the inhibition of polar growth; consequently, these cells exhibited a coccoid morphology. This result demonstrated that DivIVA is requi...

Of the five promoters detected for the ftsZ gene in Corynebacterium glutamicum, three were located within the coding region of the upstream ftsQ gene and two within the intergenic ftsQ-ftsZ region. The most distant ftsZ promoter showed activity in Escherichia coli and controlled high-level transcriptional expression of ftsZ in C. glutamicum. Quanti...

Analysis of the complete genome sequence of Corynebacterium glutamicum indicated that, in addition to ftsI, there are eight proteins with sequence motifs that are strongly conserved in penicillin binding proteins (PBPs): four genes that code for high-molecular-weight (HMW)-PBPs (PBP1a, PBP1b, PBP2a and PBP2b), two genes encoding low-molecular-weigh...

The natural resistance mechanisms of corynebacteria to respond to the environments containing high levels of arsenic were successfully adopted to develop inexpensive and selective extractants for submicrogram amounts of arsenic. Kinetic and equilibrium characteristics were evaluated, and a preliminary exploration of the capability of these strains...

The actinomycete Corynebacterium amycolatum is a saprophytic bacterium usually associated with the human skin, but it is at present considered an emergent pathogen as it is isolated from nosocomial settings from samples of immunosuppressed patients. The conventional method to distinguish C. amycolatum from closely related species is mainly based on...

Arsenic is an extremely toxic metalloid that, when present in high concentrations, severely threatens the biota and human health. Arsenic contamination of soil, water, and air is a global growing environmental problem due to leaching from geological formations, the burning of fossil fuels, wastes generated by the gold mining industry present in unc...

In Corynebacterium glutamicum, as in many Gram-positive bacteria, the cell division gene ftsI is located at the beginning of the dcw cluster, which comprises cell division- and cell wall-related genes. Transcriptional analysis of the cluster revealed that ftsI is transcribed as part of a polycistronic mRNA, which includes at least mraZ, mraW, ftsL,...

The genes involved in gluconate catabolism (gntP and gntK) in Corynebacterium glutamicum are scattered in the chromosome, and no regulatory genes are apparently associated with them, in contrast with the organization of the gnt operon in Escherichia coli and Bacillus subtilis. In C. glutamicum, gntP and gntK are essential genes when gluconate is th...

Corynebacterium glutamicum is a Gram-positive bacterium that lacks the cell division FtsA protein and actin-like MreB proteins responsible for determining cylindrical cell shape. When the cell division ftsZ gene from C. glutamicum (ftsZ(Cg)) was cloned in different multicopy plasmids, the resulting constructions could not be introduced into C. glut...

The expression of genes coding for heterologous extracellular enzymes or proteins in corynebacteria has provided new capacities to these industrially important microorganisms, such as the use of the culture media as sources of essential amino acids and hydrolytic enzymes that can be used as complements in animal food or for the production of enzyme...

Corynebacterium glutamicum is able to grow in media containing up to 12 mM arsenite and 500 mM arsenate and is one of the most arsenic-resistant microorganisms described to date. Two operons (ars1 and ars2) involved in arsenate and arsenite resistance have been identified in the complete genome sequence of Corynebacterium glutamicum. The operons ar...

In Brevibacterium lactofermentum, as in many Gram-positive bacteria, a divIVA gene is located downstream from the dcw cluster of cell-division- and cell-wall-related genes. This gene (divIVA(BL)) is mostly expressed during exponential growth, and the protein encoded, DivIVA(BL,) bears some sequence similarity to antigen 84 (Ag84) from mycobacteria...

The mobilization of plasmids from gram-negative Escherichia coli to gram-positive Brevibacterium lactofermentum, mediated by P-type transfer functions, was used to construct disrupted mutants blocked specifically in the homoserine branch of the aspartate pathway. The mutant strain B. lactofermentum R31 showed an efficiency of conjugal transfer two...

Conjugative transfer of mobilizable derivatives of the Escherichia coli narrow-host-range plasmids pBR322, pBR325, pACYC177, and pACYC184 from E. coli to species of the gram-positive genera Corynebacterium and Brevibacterium resulted in the integration of the plasmids into the genomes of the recipient bacteria. Transconjugants appeared at low frequ...

A 6.5 kb DNA fragment containing the gene (thrC) encoding threonine synthase, the last enzyme of the threonine biosynthetic pathway, has been cloned from the DNA of Bacillus sp. ULM1 by complementation of Escherichia coli and Brevibacterium lactofermentum thrC auxotrophs. Complementation studies showed that the thrB gene (encoding homoserine kinase...

Two genes, hom (encoding homoserine dehydrogenase) and thrB (encoding homoserine kinase), of the threonine biosynthetic pathway are clustered in the chromosome of Brevibacterium lactofermentum in the order 5' hom-thrB 3', separated by only 10 bp. The Brevibacterium thrB gene is expressed in Escherichia coli, in Brevibacterium lactofermentum, and in...

The thrC gene of Brevibacterium lactofermentum was cloned by complementation of Escherichia coli thrC auxotrophs. The gene was located by deletion mapping and complementation analysis in a 2.9-kb Sau3AI-HindIII fragment of the genome. This fragment also complemented a B. lactofermentum UL1035 threonine auxotroph that was deficient in threonine synt...

A cloned 9.6-kb fragment of Brevibacterium lactofermentum DNA, carrying the entire trp operon and upstream regulatory sequences, produces a polycistronic 7.0-kb transcript as detected by hybridization with an internal probe. The transcription start point (tsp) was identified by S1 mapping. The operator-promoter (OP) region subcloned in Escherichia...

The Brevibacterium lactofermentum argS gene, which encodes an arginyl-tRNA synthetase, was identified in the upstream region of the lysA gene. The cloned gene was sequenced; it encodes a 550-amino-acid protein with an M(r) of 59,797. The deduced amino acid sequence showed 28% identical and 49% similar residues when compared with the sequence of the...

The dapA and dapB genes, encoding, respectively, dihydrodipicolinate synthase and dihydrodipicolinate reductase, the two first enzymes of the lysine branch of the aspartic amino acid family, were cloned from the DNA of the amino acid-producing bacterium Brevibacterium lactofermentum. The two genes were clustered in a 3.5-kb Sau3AI-BamHI fragment bu...

Corynebacteria are highly sensitive to the glycopeptide antibiotic bleomycin. The bleomycin resistance gene of transposon Tn5 is expressed very efficiently in Brevibacterium lactofermentum. This gene constitutes an excellent marker for selection of transformants of corynebacteria. The bleomycin resistance gene is expressed from the same promoter as...

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Five DNA fragments carrying the thrB gene (homoserine kinase E.C. 2.7.1.39) of Brevibacterium lactofermentum were cloned by complementation of Escherichia coli thrB mutants using pBR322 as vector. All the cloned fragments contained a common 3.1 kb DNA sequence. The cloned fragments hybridized among themselves and with a 9 kb BamHI fragment of the c...

Members of the genera Corynebacterium and Brevibacterium are widely used in the production of amino acids and nucleotides, as well as in the bioconversion of steroids and in the cheese industry. In the last few years, cloning vectors have been developed in corynebacteria using replicons from endogenous plasmids and antibiotic resistance genes as se...

A screening of plasmids in 25 nonpathogenic coryneform bacteria was carried out. 11 Strains showed at least one plasmid, ranging in size from 4.2 to 55 kb. These plasmids did not encode bacteriocin production or resistance to a number of antibiotics or to ions such as arsenite, mercury(II) and cobalt(II). A detailed study of plasmid pBL100 from Bre...