Repurposing cetylpyridinium chloride and domiphen bromide as phosphoethanolamine transferase inhibitor to combat colistin-resistant Enterobacterales.

The emergence of plasmid-encoded colistin resistance mechanisms, MCR-1, a phosphoethanolamine transferase, rendered colistin ineffective as last resort antibiotic against severe infections caused by clinical Gram-negative bacterial pathogens. Through screening FDA-approved drug library, we identified two structurally similar compounds, namely cetylpyridinium chloride (CET) and domiphen bromide (DOM), which potentiated colistin activity in both colistin-resistant and susceptible Enterobacterales. These compounds were found to insert their long carbon chain to a hydrophobic pocket of bacterial phosphoethanolamine transferases including MCR-1, competitively blocking the binding of lipid A tail for substrate recognition and modification, resulting in the increase of bacterial sensitivity to colistin.

Heterogenous Expression and Purification of Lipid II Flippase from .

Background: is a common pathogen with strains that are resistant to existing antibiotics. MurJ from (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target.

Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action.

Twenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 μg/mL, and RA-N8 killed E.

Spatial engineering of single-atom Fe adjacent to Cu-assisted nanozymes for biomimetic O activation.

The precise design of single-atom nanozymes (SAzymes) and understanding of their biocatalytic mechanisms hold great promise for developing ideal bio-enzyme substitutes. While considerable efforts have been directed towards mimicking partial bio-inspired structures, the integration of heterogeneous SAzymes configurations and homogeneous enzyme-like mechanism remains an enormous challenge. Here, we show a spatial engineering strategy to fabricate dual-sites SAzymes with atomic Fe active center and adjacent Cu sites.

Fluorescently Modified NDM-1: A Versatile Drug Sensor for Rapid β-Lactam Antibiotic and Inhibitor Screening.

We successfully developed a fluorescent drug sensor from clinically relevant New Delhi metallo-β-lactamase-1 (NDM-1). The F70 residue was chosen to be replaced with a cysteine for conjugation with thiol-reactive fluorescein-5-maleimide to form fluorescent F70Cf, where "f" refers to fluorescein-5-maleimide. Our proteolytic studies of unlabeled F70C and labeled F70Cf monitored by electrospray ionization-mass spectrometry (ESI-MS) revealed that fluorescein-5-maleimide was specifically linked to C70 in 1:1 mole ratio (F70C:fluorophore).

Development of a bioengineered Erwinia chrysanthemi asparaginase to enhance its anti-solid tumor potential for treating gastric cancer.

Asparaginase has been traditionally applied for only treating acute lymphoblastic leukemia due to its ability to deplete asparagine. However, its ultimate anticancer potential for treating solid tumors has not yet been unleashed. In this study, we bioengineered Erwinia chrysanthemi asparaginase (ErWT), one of the US Food and Drug Administration-approved types of amino acid depleting enzymes, to achieve double amino acid depletions for treating a solid tumor.

An emerging direction for nanozyme design: from single-atom to dual-atomic-site catalysts.

Nanozymes, a new class of functional nanomaterials with enzyme-like characteristics, have recently made great achievements and have become potential substitutes for natural enzymes. In particular, single-atomic nanozymes (Sazymes) have received intense research focus on account of their versatile enzyme-like performances and well-defined spatial configurations of single-atomic sites. More recently, dual-atomic-site catalysts (DACs) containing two neighboring single-atomic sites have been explored as next-generation nanozymes, thanks to the flexibility in tuning active sites by various combinations of two single-atomic sites.

Beta-Lactam Antibiotics Can Be Measured in the Exhaled Breath Condensate in Mechanically Ventilated Patients: A Pilot Study.

Different techniques have been proposed to measure antibiotic levels within the lung parenchyma; however, their use is limited because they are invasive and associated with adverse effects. We explore whether beta-lactam antibiotics could be measured in exhaled breath condensate collected from heat and moisture exchange filters (HMEFs) and correlated with the concentration of antibiotics measured from bronchoalveolar lavage (BAL). We designed an observational study in patients undergoing mechanical ventilation, which required a BAL to confirm or discard the diagnosis of pneumonia.

The structural integrity of the membrane-embedded bacterial division complex FtsQBL studied with molecular dynamics simulations.

The FtsQBL is an essential molecular complex sitting midway through bacterial divisome assembly. To visualize and understand its structure, and the consequences of its membrane anchorage, we produced a model of the complex using the deep-learning prediction utility, AlphaFold 2. The heterotrimeric model was inserted into a 3-lipid model membrane and subjected to a 500-ns atomistic molecular dynamics simulation.

A novel ESKAPE-sensitive peptide with enhanced stability and its application in controlling multiple bacterial contaminations in chilled fresh pork.

The co-existence of various pathogenic bacteria on the surface of pork products exacerbates difficulties in food safety control. Developing broad-spectrum and stable antibacterial agents that are not antibiotics is an unmet need. To address this issue, all l-arginine residues of a reported peptide (IIRR)-NH (zp80) were substituted with the corresponding D enantiomers.

Gossypol acetate: A natural polyphenol derivative with antimicrobial activities against the essential cell division protein FtsZ.

Antimicrobial resistance has attracted worldwide attention and remains an urgent issue to resolve. Discovery of novel compounds is regarded as one way to circumvent the development of resistance and increase the available treatment options. Gossypol is a natural polyphenolic aldehyde, and it has attracted increasing attention as a possible antibacterial drug.

The crystal structure of the H116Q mutant of NDM-1: An enzyme devoid of zinc ions.

New Delhi metallo-β-lactamase 1 (NDM-1) is an important causative factor of antimicrobial resistance due to its efficient hydrolysis of a broad range of β-lactam compounds. The two zinc ions at the active site play essential roles in the NDM-1 catalytic activities. In a previous work, H116, one of the three ligands at the Zn1 site, was mutated in order to investigate the nature of zinc ion chelation.

C-terminal modification of a de novo designed antimicrobial peptide via capping of macrolactam rings.

In this work, by capping a macrolactam ring at the C-terminus of a de novo-designed peptide, namely zp80, we have constructed a small peptide library via the solid phase peptide synthesis for screening. Eight peptides bearing different aspartic acid-rich macrolactam rings but the same linear (IIRR) unit exhibited improved antibacterial activities, hemolytic activity, and selectivity index. Mechanistic studies revealed that they could destroy the integrity of bacterial envelope, leading to cytoplasm leakage and rapid dissipation of membrane potential.

Rational design and structural engineering of heterogeneous single-atom nanozyme for biosensing.

Nanozymes, an emerging family of heterogeneous nanomaterials with enzyme-like characteristics, offer significant advantages as alternatives to natural enzymes for diverse biocatalytic applications. Nevertheless, the inhomogeneous configuration of nanomaterials makes it extremely challenging to develop nanozymes of desired performance and reaction mechanism. Single-atom nanozymes (SAzymes) that are composed of single-atomic active sites may provide an answer to these challenges with remarkable enzyme-like activity and specificity.

NDM-1 Zn1-binding residue His116 plays critical roles in antibiotic hydrolysis.

Bacteria expressing NDM-1 have been labeled as superbugs because it confers upon them resistance to a broad range of β-lactam antibiotics. The enzyme has a di‑zinc active centre, with the Zn2 site extensively studied. The roles of active-site Zn1 ligand residues are, however, still not fully understood.

The structural dynamics of full-length divisome transmembrane proteins FtsQ, FtsB, and FtsL in FtsQBL complex formation.

FtsQBL is a transmembrane protein complex in the divisome of Escherichia coli that plays a critical role in regulating cell division. Although extensive efforts have been made to investigate the interactions between the three involved proteins, FtsQ, FtsB, and FtsL, the detailed interaction mechanism is still poorly understood. In this study, we used hydrogen-deuterium exchange mass spectrometry to investigate these full-length proteins and their complexes.

Specific Amino Acid Substitutions in OXA-51-Type -Lactamase Enhance Catalytic Activity to a Level Comparable to Carbapenemase OXA-23 and OXA-24/40.

The chromosomal -type gene encodes carbapenem-hydrolyzing class D β-lactamases (CHDLs), specific variants shown to mediate carbapenem resistance in the Gram-negative bacterial pathogen . This study aims to characterize the effect of key amino acid substitutions in OXA-51 variants of carbapenem-hydrolyzing class D β-lactamases (CHDLs) on substrate catalysis. Mutational and structural analyses indicated that each of the L167V, W222G, or I129L substitutions contributed to an increase in catalytic activity.

Rational structural modification of the isatin scaffold to develop new and potent antimicrobial agents targeting bacterial peptidoglycan glycosyltransferase.

A series of isatin derivatives bearing three different substituent groups at the N-1, C-3 and C-5 positions of the isatin scaffold were systematically designed and synthesized to study the structure-activity relationship of their inhibition of bacterial peptidoglycan glycosyltransferase (PGT) activity and antimicrobial susceptibility against , and methicillin-resistant (MRSA (BAA41)) strains. The substituents at these sites are pointing towards three different directions from the isatin scaffold to interact with the amino acid residues in the binding pocket of PGT. Comparative studies of their structure-activity relationship allow us to gain better understanding of the direction of the substituents that contribute critical interactions leading to inhibition activity against the bacterial enzyme.

Discovery of FtsZ inhibitors by virtual screening as antibacterial agents and study of the inhibition mechanism.

Inhibition of bacterial cell division is a novel mechanistic action in the development of new antimicrobial agents. The FtsZ protein is an important antimicrobial drug target because of its essential role in bacterial cell division. In the present study, potential inhibitors of FtsZ were identified by virtual screening followed by and bioassays.

Scattering asymmetry and circular dichroism in coupled PT-symmetric chiral nanoparticles.

We investigate the scattering properties of coupled parity-time (PT) symmetric chiral nanospheres with scattering matrix formalism. The exceptional points, i.e.

High-Q localized surface plasmon resonance based on bound states in the continuum for enhanced refractive index sensing.

Nanophotonics based on localized surface plasmon resonance (LSPR) has emerged as a vibrant arena for research into enhanced light-matter interactions with potential applications in imaging, sensing, and computing. However, the low quality (Q) factor of LSPR is a significant barrier to comprehensive device applications. Here, we demonstrate that coupling the LSPR of a gold nanowire array with the optical bound states in the continuum (BIC) of a dielectric double-layer grating can significantly increase the Q factor of LSPR.

Long-Range Directional Routing and Spatial Selection of High-Spin-Purity Valley Trion Emission in Monolayer WS.

Valley-dependent excitation and emission in transition metal dichalcogenides (TMDCs) have recently emerged as a new avenue for optical data manipulation, quantum optical technologies, and chiral photonics. The valley-polarized electronic states can be optically addressed through photonic spin-orbit interaction of excitonic emission, typically with plasmonic nanostructures, but their performance is limited by the low quantum yield of neutral excitons in TMDC multilayers and the large Ohmic loss of plasmonic systems. Here, we demonstrate a valleytronic system based on the trion emission in high-quantum-yield WS monolayers chirally coupled to a low-loss microfiber.

Improving the performance stability of direct seawater electrolysis: from catalyst design to electrode engineering.

Direct seawater electrolysis opens a new opportunity to lower the cost of hydrogen production from current water electrolysis technologies. To facilitate its commercialization, the challenges of long-term performance stability of electrochemical devices need to be first addressed and realized. This minireview summarised the common causes of performance decline during seawater electrolysis, from chemical reactions at the electrode surface to physical damage to the cell.