Enzymatic Synthesis of Biologically Active -Phosphinic Analogue of α-Ketoglutarate.

Amino acid analogues with a phosphorus-containing moiety replacing the carboxylic group are promising sources of biologically active compounds. The -phosphinic group, with hydrogen-phosphorus-carbon (H-P-C) bonds and a flattened tetrahedral configuration, is a bioisostere of the carboxylic group. Consequently, amino--phosphinic acids undergo substrate-like enzymatic transformations, leading to new biologically active metabolites.

Integrated multi-omics unveil the impact of H-phosphinic analogs of glutamate and α-ketoglutarate on Escherichia coli metabolism.

Desmethylphosphinothricin (L-Glu-γ-P) is the H-phosphinic analog of glutamate with carbon-phosphorus-hydrogen (C-P-H) bonds. In L-Glu-γ-P the phosphinic group acts as a bioisostere of the glutamate γ-carboxyl group allowing the molecule to be a substrate of Escherichia coli glutamate decarboxylase, a pyridoxal 5'-phosphate-dependent α-decarboxylase. In addition, the L-Glu-γ-P decarboxylation product, GABA-P, is further metabolized by bacterial GABA-transaminase, another pyridoxal 5'-phosphate-dependent enzyme, and succinic semialdehyde dehydrogenase, a NADP-dependent enzyme.

Synthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant Glutamate Decarboxylase.

-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the -homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of -homocysteinesulfinic acid (-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities.

Multifunctional FFP2 Face Mask for White Light Disinfection and Pathogens Detection using Hybrid Nanostructures and Optical Metasurfaces.

A new generation of an FFP2 (Filtering Face Piece of type 2) smart face mask is achieved by integrating broadband hybrid nanomaterials and a self-assembled optical metasurface. The multifunctional FFP2 face mask shows simultaneously white light-assisted on-demand disinfection properties and versatile biosensing capabilities. These properties are achieved by a powerful combination of white light thermoplasmonic responsive hybrid nanomaterials, which provide excellent photo-thermal disinfection properties, and optical metasurface-based colorimetric biosensors, with a very low limit of pathogens detection.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges.

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs.

Exploitation of microbial activities at low pH to enhance planetary health.

Awareness is growing that human health cannot be considered in isolation but is inextricably woven with the health of the environment in which we live. It is, however, under-recognized that the sustainability of human activities strongly relies on preserving the equilibrium of the microbial communities living in/on/around us. Microbial metabolic activities are instrumental for production, functionalization, processing, and preservation of food.

A Desmethylphosphinothricin Dipeptide Derivative Effectively Inhibits and Growth.

New antibiotics are unquestionably needed to fight the emergence and spread of multidrug-resistant bacteria. To date, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-P), an analogue of glutamate with a phosphinic moiety replacing the γ-carboxyl group, we previously showed its promising antibacterial activity on .

White light thermoplasmonic activated gold nanorod arrays enable the photo-thermal disinfection of medical tools from bacterial contamination.

The outspread of bacterial pathogens causing severe infections and spreading rapidly, especially among hospitalized patients, is worrying and represents a global public health issue. Current disinfection techniques are becoming insufficient to counteract the spread of these pathogens because they carry multiple antibiotic-resistance genes. For this reason, a constant need exists for new technological solutions that rely on physical methods rather than chemicals.

Physical, chemical, and sensory properties of water kefir produced from juice and pomace.

Water kefir is widely consumed all over the world due to its potential health benefits. The aim of this current study was to compare non-fermented juice and fermented beverage of water kefir produced from juice and pomace in terms of chemical, physical and sensory quality as well as valorisation of pomace in the production of water kefir. When compared to water kefir made with aronia juice, less reduction in total phenolic content (TPC), total flavonoid content (TFC) and total anthocyanin content (TAC) was observed in samples made with aronia pomace during the fermentation process.

Antibacterial Activity of Peptide Derivatives of Phosphinothricin against Multidrug-Resistant .

The fast spread of bacteria that are resistant to many classes of antibiotics (multidrug resistant) is a global threat to human and animal health with a worrisome scenario ahead. Novel therapeutical strategies are of crucial importance to combat this phenomenon. For this purpose, we investigated the antimicrobial properties of the naturally occurring tripeptide Bialaphos and a dipeptide -leucyl--phosphinoithricin, the synthesis and diastereomers separation of which are herein described.

A COST Action on microbial responses to low pH: Developing links and sharing resources across the academic-industrial divide.

We present work of our COST Action on "Understanding and exploiting the impacts of low pH on micro-organisms". First, we summarise a workshop held at the European Federation of Biotechnology meeting on Microbial Stress Responses (online in 2020) on "Industrial applications of low pH stress on microbial bio-based production", as an example of an initiative fostering links between pure and applied research. We report the outcomes of a small survey on the challenging topic of developing links between researchers working in academia and industry that show that, while people in different sectors strongly support such links, barriers remain that obstruct this process.

Impact of the Gastrointestinal Tract Microbiota on Cardiovascular Health and Pathophysiology.

The microbiota of the gastrointestinal tract (GIT) is an extremely diverse community of microorganisms, and their collective genomes (microbiome) provide a vast arsenal of biological activities, particularly enzymatic ones, which are far from being fully elucidated. The study of the microbiota (and the microbiome) is receiving great interest from the biomedical community because it carries the potential to improve risk prediction models, refine primary and secondary prevention efforts, and also design more appropriate and personalized therapies, including pharmacological ones. A growing body of evidence, although sometimes impaired by the limited number of subjects involved in the studies, suggests that GIT dysbiosis, that is, the altered microbial composition, has an important role in causing and/or worsening cardiovascular disease (CVD).

Landscape of Stress Response and Virulence Genes Among Strains.

The pathogenic microorganism is ubiquitous and responsible for listeriosis, a disease with a high mortality rate in susceptible people. It can persist in different habitats, including the farm environment, the food production environments, and in foods. This pathogen can grow under challenging conditions, such as low pH, low temperatures, and high salt concentrations.

Essential oils from species inhibit biofilm formation and the virulence of EPEC 2348/69.

Enteropathogenic E2346/69 (EPEC) has caused foodborne outbreaks worldwide and the bacterium forms antimicrobial-tolerant biofilms. The anti-biofilm formation of various components of essential oils extracted from selected medicinal plants were investigated and tested on EPEC and wild strains of . Oils extracted from the family Asteraceae and their major common constituents at 0.

Understanding How Microorganisms Respond to Acid pH Is Central to Their Control and Successful Exploitation.

Microbes from the three domains of life, , , and , share the need to sense and respond to changes in the external and internal concentrations of protons. When the proton concentration is high, acidic conditions prevail and cells must respond appropriately to ensure that macromolecules and metabolic processes are sufficiently protected to sustain life. While, we have learned much in recent decades about the mechanisms that microbes use to cope with acid, including the unique challenges presented by organic acids, there is still much to be gained from developing a deeper understanding of the effects and responses to acid in microbes.

Enzymatic kinetic resolution of desmethylphosphinothricin indicates that phosphinic group is a bioisostere of carboxyl group.

Escherichia coli glutamate decarboxylase (EcGadB), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, is highly specific for L-glutamate and was demonstrated to be effectively immobilised for the production of γ-aminobutyric acid (GABA), its decarboxylation product. Herein we show that EcGadB quantitatively decarboxylates the L-isomer of D,L-2-amino-4-(hydroxyphosphinyl)butyric acid (D,L-Glu-γ-P), a phosphinic analogue of glutamate containing C-P-H bonds. This yields 3-aminopropylphosphinic acid (GABA-P), a known GABA receptor agonist and provides previously unknown D-Glu-γ-P, allowing us to demonstrate that L-Glu-γ-P, but not D-Glu-γ-P, is responsible for D,L-Glu-γ-P antibacterial activity.

Lethality of in a murine model of infection depends on the gene involved in O-polysaccharide synthesis.

was isolated a decade ago from wildlife and soil in Europe. Compared to the classical species, it exhibits atypical virulence properties such as increased growth in human and murine macrophages and lethality in experimentally infected mice. A spontaneous rough (R) mutant strain, derived from the smooth reference strain CCM4915, showed increased macrophage colonization and was non-lethal in murine infections.

The Glutaminase-Dependent Acid Resistance System: Qualitative and Quantitative Assays and Analysis of Its Distribution in Enteric Bacteria.

Neutralophilic bacteria have developed several strategies to overcome the deleterious effects of acid stress. In particular, the amino acid-dependent systems are widespread, with their activities overlapping, covering a rather large pH range, from 6 to <2. Recent reports showed that an acid resistance (AR) system relying on the amino acid glutamine (AR2_Q), the most readily available amino acid in the free form, is operative in , and some species.

The Glutaminase-Dependent System Confers Extreme Acid Resistance to New Species and Atypical Strains of .

Neutralophilic bacteria have developed specific mechanisms to cope with the acid stress encountered in environments such as soil, fermented foods, and host compartments. In , the glutamate decarboxylase (Gad)-dependent system is extremely efficient: it requires the concerted action of glutamate decarboxylase (GadA/GadB) and of the glutamate (Glu)/γ-aminobutyrate antiporter, GadC. Notably, this system is operative also in new strains/species of , among which , but not in the "classical" species, with the exception of marine mammals strains.

The gene codes for an inner membrane protein involved in GABA export in .

In order to survive the exposure to acid pH, activates molecular circuits leading from acid tolerance to extreme acid resistance (AR). The activation of the different circuits involves several global and specific regulators affecting the expression of membrane, periplasmic and cytosolic proteins acting at different levels to dampen the harmful consequences of the uncontrolled entry of protons intracellularly. Many genes coding for the structural components of the AR circuits (protecting from pH ≤ 2.

The Escherichia coli Acid Stress Response and Its Significance for Pathogenesis.

Escherichia coli has a remarkable ability to survive low pH and possesses a number of different genetic systems that enable it to do this. These may be expressed constitutively, typically in stationary phase, or induced by growth under a variety of conditions. The activities of these systems have been implicated in the ability of E.

Biochemical and spectroscopic properties of Brucella microti glutamate decarboxylase, a key component of the glutamate-dependent acid resistance system.

In orally acquired bacteria, the ability to counteract extreme acid stress (pH ⩽ 2.5) ensures survival during transit through the animal host stomach. In several neutralophilic bacteria, the glutamate-dependent acid resistance system (GDAR) is the most efficient molecular system in conferring protection from acid stress.