A5021690286- Trace Elements in Health
- Metal-Catalyzed Oxygenation Mechanisms
- Salmonella and Campylobacter epidemiology
- Iron Metabolism and Disorders
- Radioactive element chemistry and processing
- Metal complexes synthesis and properties
- Antibiotic Resistance in Bacteria
- Glutathione Transferases and Polymorphisms
- Drug Transport and Resistance Mechanisms
- Environmental Toxicology and Ecotoxicology
- CO2 Reduction Techniques and Catalysts
- Vibrio bacteria research studies
- Bacterial biofilms and quorum sensing
- Porphyrin Metabolism and Disorders
- Genomics, phytochemicals, and oxidative stress
- Electrochemical Analysis and Applications
- Cholinesterase and Neurodegenerative Diseases
- Cystic Fibrosis Research Advances
- Viral gastroenteritis research and epidemiology
- Metalloenzymes and iron-sulfur proteins
- Neurological diseases and metabolism
- Animal Virus Infections Studies
- Hemoglobin structure and function
- Bacterial Genetics and Biotechnology
- Plant Micronutrient Interactions and Effects
University of Rome Tor Vergata
2016-2025
SLAC National Accelerator Laboratory
2016-2020
Stanford University
2018
Istituto Nazionale Biostrutture e Biosistemi
2008-2016
In-Q-Tel
2015-2016
Elettra-Sincrotrone Trieste S.C.p.A.
2014-2015
University of Trieste
2015
Institute of Biostructure and Bioimaging
2008-2009
Centre National de la Recherche Scientifique
2005-2008
Park University
2008
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand libraries can access far greater space, provided that the predictive accuracy sufficient useful Through largest and most diverse virtual HTS campaign reported date, comprising 318 individual projects, we demonstrate our AtomNet® convolutional neural network...
To investigate the relevance of zinc in host-pathogen interactions, we have constructed Salmonella enterica mutant strains which znuA gene, encodes periplasmic component ZnuABC high-affinity Zn2+ transporter, was deleted. This mutation does not alter ability to grow rich media but drastically reduces its multiply deprived zinc. In agreement with this phenotype, ZnuA accumulates only bacteria cultivated environments poor spite nearly millimolar intracellular concentration zinc, found that is...
We have set up a model system for familial amyotrophic lateral sclerosis (FALS) by transfecting human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type Cu,Zn superoxide dismutase (Cu,ZnSOD) or mutant this enzyme (G93A) associated FALS. tested mitochondrial function and determined cytosolic Ca2+ concentration in control cells (untransfected) expressing Cu,ZnSOD G93A. report that G93A induces significant loss membrane potential, an increased...
Organic chromophores with heteroatoms possess an important excited state relaxation channel from optically allowed {\pi}{\pi}* to a dark n{\pi}*state. We exploit the element and site specificity of soft x-ray absorption spectroscopy selectively follow electronic change during {\pi}{\pi}*/n{\pi}* internal conversion. As hole forms in n orbital conversion, near edge fine structure (NEXAFS) spectrum at heteroatom K-edge exhibits additional resonance. demonstrate concept nucleobase thymine,...
Previous studies have suggested that P. aeruginosa possesses redundant zinc uptake systems. To identify uncharacterized transporters, we analyzed the genome-wide transcriptional responses of PA14 to restriction. This approach led identification an operon (zrmABCD) regulated by regulator Zur, encodes for a metallophore-mediated import system. includes genes TonB-dependent Outer Membrane Protein (ZrmA) and putative nicotianamine synthase (ZrmB). The simultaneous inactivation ZnuABC transporter...
The pathways ensuring the efficient uptake of zinc are crucial for ability bacteria to multiply in infected host. To better understand bacterial responses deficiency, we have investigated role periplasmic protein ZinT Salmonella enterica serovar Typhimurium. We found that zinT expression is regulated by Zur and parallels ZnuA, component transporter ZnuABC. Despite fact contributes growth media containing little zinc, disruption does not significantly affect virulence mice. became clear using...
Zinc is an essential element for all living cells. Recent studies have shown that the ZnuABC zinc uptake system significantly contributes to ability of several pathogens multiply in infected host and cause disease, suggesting scarcely available within different tissues host. To better understand role bacterial pathogenicity, we undertaken a functional characterization ZnuABC-mediated pathway enterohemorrhagic Escherichia coli O157:H7.In this work analyzed expression metal ZnuA, periplasmic...
Salmonella enterica serovar Typhimurium is an important zoonotic gastrointestinal pathogen responsible for foodborne disease worldwide. It a successful enteric because it has developed virulence strategies allowing to survive in highly inflamed intestinal environment exploiting inflammation overcome colonization resistance provided by microbiota. In this study, we used piglets featuring intact microbiota, which naturally develop gastroenteritis, as model salmonellosis. We compared the...
Pseudomonas aeruginosa and Burkholderia cenocepacia are predominant opportunistic pathogens in cystic fibrosis (CF) patients. In healthy humans the lower respiratory tract as well all mucosa, contains a very low free iron concentration (10(-18) M), while CF patients sputum is high, showing median value of 63x10(-6) M. Accumulation catalytic reactive heavily contributes to subsequent clinical complications lung disorders by production oxygen species increases bacterial growth virulence. The...
Zinc is an essential metal for cellular homeostasis and function in both eukaryotes prokaryotes. To acquire this nutrient, bacteria employ transporters characterized by different affinity the metal. Several studies have investigated role of high transporter ZnuABC bacterial response to zinc shortage, showing that has a key adapting starvation. In contrast, low importer ZupT been subject limited investigations. Here we show Salmonella strain lacking impaired its ability grow devoid...
The ability of a large number bacterial pathogens to multiply in the infected host and cause disease is dependent on their express high affinity zinc importers. In many bacteria, ZnuABC, transporter ABC family, plays central role process uptake poor environments, including tissues host. To initiate an investigation into relevance apparatus for Pseudomonas aeruginosa pathogenicity, we have generated znuA mutant PA14 strain. We found that this strain displays limited growth defect depleted...
Over the past decades, Salmonella 4,[5],12:i:- has rapidly emerged and it is isolated with high frequency in swine food chain. Although many studies have documented epidemiological success of this serovar, few investigations tried to explain phenomenon from a genetic perspective. Here comparative whole-genome analysis 50 epidemiologically unrelated S. 4,[5],12:i:-, Italy 2010-2016 was performed, characterizing them terms elements potentially conferring resistance, tolerance persistence...
The sodC-encoded Mycobacterium tuberculosis superoxide dismutase (SOD) shows high sequence homology to other members of the copper/zinc-containing SOD family. Its three-dimensional structure is reported here, solved by x-ray crystallography at 1.63-Å resolution. Metal analyses recombinant protein indicate that native form enzyme lacks zinc ion, which has a very important structural and functional role in all known enzymes this class. absence within active site due significant rearrangements...
In the human placental glutathione transferase, Cys-47 possesses, at physiological pH values, a pKavalue of 4.2 and may exist as an ion pair with protonated ɛ-amino group Lys-54. Using site-directed mutagenesis we investigate spectral, kinetic, structural properties Lys-54 mutants. The results shown indicate that thiolate detected 229 nm should be assigned exclusively to Cys-47. contribution activation is assessed by spectral K54A mutant enzyme. induced cooperativity toward glutathione,...
Several point mutations in the gene coding for human Cu,Zn superoxide dismutase have been reported as being responsible familial amyotrophic lateral sclerosis (FALS). However, no direct demonstration has provided a correlation between total activity and severity of FALS pathology. In order to get better insight into mechanism (s) underlying phenotype, we investigated copper binding properties single mutant H46R, which is associated with Japanese form FALS. We shown that this structurally...
Many of the most virulent strains Salmonella enterica produce two distinct Cu,Zn-superoxide dismutases (SodCI and SodCII). The bacteriophage-encoded SodCI enzyme makes greater contribution to virulence. We have performed a detailed comparison functional, structural, regulatory properties SodC enzymes. Here we demonstrate that SodCII differ with regard specific activity, protease resistance, metal affinity, peroxidative dimeric exhibiting superior stability activity. In particular, monomeric...