- Antibiotic Resistance in Bacteria
- Photosynthetic Processes and Mechanisms
- Bacterial biofilms and quorum sensing
- Vibrio bacteria research studies
- Antibiotics Pharmacokinetics and Efficacy
- Trace Elements in Health
- Infections and bacterial resistance
- Enzyme Structure and Function
- Retinal Development and Disorders
- Metal-Catalyzed Oxygenation Mechanisms
- Electrochemical Analysis and Applications
- Tuberculosis Research and Epidemiology
- Photoreceptor and optogenetics research
- Pharmaceutical and Antibiotic Environmental Impacts
- Pneumocystis jirovecii pneumonia detection and treatment
- Bacterial Genetics and Biotechnology
- Molecular spectroscopy and chirality
- Electrochemical sensors and biosensors
- Cassava research and cyanide
- Enzyme Production and Characterization
- Neuroscience and Neuropharmacology Research
- Porphyrin and Phthalocyanine Chemistry
- Metal complexes synthesis and properties
- Mitochondrial Function and Pathology
- Protein Structure and Dynamics
Consejo Nacional de Investigaciones Científicas y Técnicas
2016-2025
Instituto de Biología Molecular y Celular de Rosario
2016-2025
National University of Rosario
2016-2025
Louis Stokes Cleveland VA Medical Center
2017-2025
United States Department of Veterans Affairs
2004-2023
Universidade da Coruña
2022
The University of Texas Health Science Center at Houston
2007-2021
The University of Texas MD Anderson Cancer Center
2021
Instituto de Ciências Farmacêuticas
2020
Centro Científico Tecnólogico - Rosario
2018-2019
Based upon knowledge of the hydrolytic profile major β-lactamases found in Gram-negative bacteria, we tested efficacy combination ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine vitro a unique CAZ-AVI ATM 21 representative Enterobacteriaceae isolates complex molecular background that included...
Abstract Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that S1P levels rapidly increase 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing 16 days concurrently elevated sphingonisne kinase (Sphk1) activity haemoglobin (Hb) oxygen (O 2 ) release capacity. Mouse genetic...
Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, B3), complicating development of βLIs effective against enzymes. Bisthiazolidines (BTZs) carboxylate-containing, bicyclic compounds, considered as penicillin analogs with an additional free thiol. Here, we show both l- d-BTZ enantiomers micromolar competitive MBL in vitro, Kis 6-15 µM...
Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) the main mechanism of resistance against carbapenems. Clinically approved inhibitors MBLs currently unavailable as design has been limited incomplete knowledge their mechanism. Here, we report a biochemical and biophysical study carbapenem hydrolysis B1 enzymes NDM-1 BcII in bi-Zn(II) form, mono-Zn(II) B2 Sfh-I B3 GOB-18. These...
Pathogenic Gram-negative bacteria resistant to almost all β-lactam antibiotics are a major public health threat. Zn(II)-dependent or metallo-β-lactamases (MBLs) produced by these inactivate most antibiotics, including the carbapenems, which "last line therapies" for life-threatening infections. NDM-1 is carbapenemase belonging MBL family that rapidly spreading worldwide. Regrettably, inhibitors of MBLs not yet developed. Here we present bisthiazolidine (BTZ) scaffold as structure with some...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe iron-sulfur cluster (Fe4S4) centers in ferredoxins studied through proton and carbon hyperfine coupling. Sequence-specific assignments of cysteines from Clostridium acidi urici pasteurianumIvano Bertini, Francesco Capozzi, Claudio Luchinat, Mario Piccioli, Alejandro J. VilaCite this: Am. Chem. Soc. 1994, 116, 2, 651–660Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January...
Protein evolution is crucial for organismal adaptation and fitness. This process takes place by shaping a given 3-dimensional fold its particular biochemical function within the metabolic requirements constraints of environment. The complex interplay between sequence, structure, functionality, stability that gives rise to phenotype has limited identification traits acquired through evolution. further complicated fact mutations are pleiotropic, interactions not always understood. Antibiotic...
Cytochrome c, a mitochondrial electron transfer protein containing hexacoordinated heme, is involved in other physiologically relevant events, such as the triggering of apoptosis, and activation peroxidatic activity. The latter occurs secondary to interactions with cardiolipin and/or post-translational modifications, including tyrosine nitration by peroxynitrite nitric oxide-derived oxidants. gain activity nitrated cytochrome c has been related heme site transition physiological pH region,...
The production of β-lactamase enzymes is one the most distributed resistance mechanisms towards β-lactam antibiotics. Metallo-β-lactamases constitute a worrisome group these kinds enzymes, since they present broad spectrum profile, being able to hydrolyze not only penicillins, but also latest generation cephalosporins and carbapenems, which at last resource VIM, IMP, NDM comprise main groups clinically relevant metallo-β-lactamases. Here we an update features natural variants that have...
ABSTRACT Elizabethkingia meningoseptica , a Gram-negative rod widely distributed in the environment, is resistant to most β-lactam antibiotics. Three bla genes have been identified E. coding for extended-spectrum serine-β-lactamase CME (class D) and two unrelated wide-spectrum metallo-β-lactamases, BlaB (subclass B1) GOB B3). singular being only reported microorganism possessing chromosomally encoded MBL genes. Real-time PCR biochemical analysis demonstrate that three are actively expressed...
Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading and taking a staggering toll on all health care systems, largely due to the dissemination of genes coding for potent carbapenemases. An important family carbapenemases Zn(II)-dependent β-lactamases, known as metallo-β-lactamases (MBLs). Among them, New Delhi metallo-β-lactamase (NDM) has experienced fastest widest geographical spread. While other clinically MBLs soluble periplasmic enzymes, NDMs lipoproteins anchored outer...
Abstract The worldwide dissemination of metallo-β-lactamases (MBLs), mediating resistance to carbapenem antibiotics, is a major public health problem. extent MBLs such as VIM-2, SPM-1 and NDM among Gram-negative pathogens cannot be explained solely based on the associated mobile genetic elements or phenotype. Here, we report that MBL host range determined by impact expression bacterial fitness. signal peptide sequence dictates their adaptability each host. In uncommon hosts, inefficient...
Multiple antibiotic resistance mechanisms, including two β-lactamases, L1, a metallo-β-lactamase, and L2, class A cephalosporinase, make S. maltophilia naturally multidrug resistant. Thus, infections caused by pose big therapeutic challenge. Our study aims to understand the microbiological molecular characteristics of isolates recovered from human sources. highlight profile this collection is excellent activity ceftazidime-avibactam aztreonam combination. We hope result prompts controlled...
Understanding the driving forces behind protein evolution requires ability to correlate molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present study all possible evolutionary pathways leading metallo-β-lactamase variant optimized by directed evolution. By studying activity, stability and binding capabilities mutants in preferred...
Significance Cellular respiration in humans depends on the correct assembly of a copper site (Cu A ) cytochrome oxidases. Because is toxic at high levels, cells require specific mechanisms to regulate transport and delivery. Two proteins from Sco family are involved this mechanism human mitochondria, mutations any these jeopardize Cu site, leading lethal pathologies newborns. We show that Sco1 protein responsible for delivering ions oxidase, with degree selectivity. Sco2, instead, provides...
Stenotrophomonas maltophilia is an emerging opportunistic pathogen, classified by the World Health Organization as one of leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for S. urgent. We demonstrate vitro efficacy aztreonam-avibactam (ATM-AVI) against and kinetically characterize inhibition L2 β-lactamase avibactam. ATM-AVI overcomes aztreonam resistance selected clinical strains maltophilia, addressing unmet medical need.