Self-Assembly of Tunable Intrinsically Disordered Peptide Amphiphiles.

Intrinsically disordered peptide amphiphiles (IDPAs) present a novel class of synthetic conjugates that consist of short hydrophilic polypeptides anchored to hydrocarbon chains. These hybrid polymer-lipid block constructs spontaneously self-assemble into dispersed nanoscopic aggregates or ordered mesophases in aqueous solution due to hydrophobic interactions. Yet, the possible sequence variations and their influence on the self-assembly structures are vast and have hardly been explored.

Consensus on β-Lactamase Nomenclature.

Assigning names to β-lactamase variants has been inconsistent and has led to confusion in the published literature. The common availability of whole genome sequencing has resulted in an exponential growth in the number of new β-lactamase genes. In November 2021 an international group of β-lactamase experts met virtually to develop a consensus for the way naturally-occurring β-lactamase genes should be named.

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles.

Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block copolymers.

Glucosylceramide Associated with Gaucher Disease Forms Amyloid-like Twisted Ribbon Fibrils That Induce α-Synuclein Aggregation.

A major risk factor for Gaucher's disease is loss of function mutations in the gene that encodes lysosomal β-glucocerebrosidase, resulting in accumulation of glucosylceramide (GlcCer), a key lysosomal sphingolipid. mutations also enhance the risk for Parkinson's disease, whose hallmark is the aggregation of α-synuclein (αSyn). However, the role of accumulated GlcCer in αSyn aggregation is not completely understood.

Escherichia coli GyrA Tower Domain Interacts with QnrB1 Loop B and Plays an Important Role in QnrB1 Protection from Quinolone Inhibition.

The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the larger loop B, of Qnr proteins are essential for quinolone protection of DNA gyrase. The specific QnrB1 interaction sites on DNA gyrase are not known.

Analyzing Possible Native Functions of the Quinolone Resistance Gene in Vibrio vulnificus.

The worldwide distribution of genes found on plasmids and their presence on the chromosomes of aquatic bacteria, such as , one of the suspected sources, suggests an origin before the development of synthetic quinolones. However, their native function remains unknown. Previous work indicated that expression of in was induced by cold shock.

Plasmids and genes contributing to high-level quinolone resistance in Escherichia coli.

Introduction: The importance of plasmid-mediated quinolone resistance (PMQR) in Enterobacterales and its high incidence has been emphasised many times. However, a clinical strain carrying more than two PMQR genes is rare. This study sequenced plasmid transconjugants from a donor strain carrying four different PMQR genes to establish their genetic locations.

Self-Assembly of Aromatic Amino Acid Enantiomers into Supramolecular Materials of High Rigidity.

Most natural biomolecules may exist in either of two enantiomeric forms. Although in nature, amino acid biopolymers are characterized by l-type homochirality, incorporation of d-amino acids in the design of self-assembling peptide motifs has been shown to significantly alter enzyme stability, conformation, self-assembly behavior, cytotoxicity, and even therapeutic activity. However, while functional metabolite assemblies are ubiquitous throughout nature and play numerous important roles including physiological, structural, or catalytic functions, the effect of chirality on the self-assembly nature and function of single amino acids is not yet explored.

Delayed nucleation in lipid particles.

Metastable states in first-order phase-transitions have been traditionally described by classical nucleation theory (CNT). However, recently an increasing number of systems displaying such a transition have not been successfully modelled by CNT. The delayed crystallization of phospholipids upon super-cooling is an interesting case, since the extended timescales allow access into the dynamics.

A Standard Numbering Scheme for Class C β-Lactamases.

Unlike for classes A and B, a standardized amino acid numbering scheme has not been proposed for the class C (AmpC) β-lactamases, which complicates communication in the field. Here, we propose a scheme developed through a collaborative approach that considers both sequence and structure, preserves traditional numbering of catalytically important residues (Ser, Lys, Tyr, and Lys), is adaptable to new variants or enzymes yet to be discovered and includes a variation for genetic and epidemiological applications.

Functional Coiled-Coil-like Assembly by Knob-into-Hole Packing of Single Heptad Repeat.

Coiled-coil peptides represent the principal building blocks for structure-based design of bionanomaterials. The sequence-structure relationship and precise nanoscale ordering of the coiled-coil helices originate from the knob-into-hole (KIH) packing of side chains. The helical interface stabilized by the KIH interaction is known to have chain lengths ranging from 30 to 1000 residues.

Cold shock induces chromosomal in species and plasmid-mediated in .

genes are found in aquatic bacteria and preceded the development of synthetic quinolones. Their natural functions are unknown. We evaluated the expression of chromosomal in species in response to environmental stresses and DNA damaging agents.

Multiple Copies of on an IncA/C Plasmid Explain Enhanced Quinolone Resistance in an Escherichia coli Mutant.

In a previous study, mutants with enhanced ciprofloxacin resistance (Cip) were selected from J53/pMG252 carrying Strain J53 Cip 8-2 showed an increase in the copy number and transcription level of We sequenced the plasmids on Illumina and MinION platforms. Parental plasmid pMG252 and plasmid pMG252A from strain J53 Cip 8-2 were almost identical, except for the region containing that in pMG252A contained 4 additional copies of the Δ-IS region.

Deciphering the Rules for Amino Acid Co-Assembly Based on Interlayer Distances.

Metabolite materials are extremely useful to obtain functional bioinspired assemblies with unique physical properties for various applications in the fields of material science, engineering, and medicine by self-assembly of the simplest biological building blocks. Supramolecular co-assembly has recently emerged as a promising extended approach to further expand the conformational space of metabolite assemblies in terms of structural and functional complexity. Yet, the design of synergistically co-assembled amino acids to produce tailor-made functional architectures is still challenging.

Transition of Metastable Cross-α Crystals into Cross-β Fibrils by β-Turn Flipping.

The ensemble of native, folded state was once considered to represent the global energy minimum of a given protein sequence. More recently, the discovery of the cross-β amyloid state revealed that deeper energy minima exist, often associated with pathogenic, fibrillar deposits, when the concentration of proteins reaches a critical value. Fortunately, a sizable energy barrier impedes the conversion from native to pathogenic states.

Genes and Proteins Involved in Induction.

Expression of the quinolone resistance gene is increased by quinolones, but unlike induction of some other genes, the bacterial SOS system is not involved and no box is found upstream. Nonetheless, at least 205 bp of upstream sequence is required for induction to take place. An upstream sequence bound to beads trapped potential binding proteins from cell extracts that were identified by mass spectrometry as Dps, Fis, Ihf, Lrp, CysB, and YjhU.

Chromosomal mutations that accompany qnr in clinical isolates of Escherichia coli.

We examined 13 qnr-positive and 14 qnr-negative clinical isolates of Escherichia coli for mutations previously seen in a qnr-containing laboratory strain exposed to supra minimum inhibitory concentrations (MICs) of ciprofloxacin. Among the qnr-positive strains, those with ciprofloxacin MICs of ≥ 2 µg/mL had at least one mutation in gyrA. Mutations in parC were present in strains with a ciprofloxacin MIC of ≥ 128 µg/mL.

Study of Plasmid-Mediated Quinolone Resistance in Bacteria.

Plasmid-mediated quinolone resistance (PMQR) involves genes for proteins that protect the quinolone targets, an enzyme that inactivates certain quinolones as well as aminoglycosides, and pumps that efflux quinolones. Quinolone susceptibility is reduced by these mechanisms but not to the level of clinical resistance unless chromosomal mutations are also present. PCR primers and conditions for PMQR gene detection are described as well as how to establish a plasmid location.

A minimal length rigid helical peptide motif allows rational design of modular surfactants.

Extensive work has been invested in the design of bio-inspired peptide emulsifiers. Yet, none of the formulated surfactants were based on the utilization of the robust conformation and self-assembly tendencies presented by the hydrophobins, which exhibited highest surface activity among all known proteins. Here we show that a minimalist design scheme could be employed to fabricate rigid helical peptides to mimic the rigid conformation and the helical amphipathic organization.

Entropic Phase Transitions with Stable Twisted Intermediates of Bio-Inspired Self-Assembly.

Controlling the hierarchical process and capturing the intermediate stage underlying bio-inspired self-assembly are pivotal for understanding their aggregation mechanism and exploring possible applications. Here, the self-assembly of a designed minimal lipopeptide was characterized, showing it to initially self-assemble to narrow nanotwists, which then ripen to wide nanotwists, and finally transit to hollow nanotubes. The supramolecular phase transitions were revealed to be driven by entropic hydrophobic interactions, rather than by the common mechanism of enthalpy-related contributions.

Design of Controllable Bio-Inspired Chiroptic Self-Assemblies.

Modulation of chiroptics, chiral phenomena of the optical properties, is pivotal in a variety of advanced applications, including chirality-specific biosensing and photonic switches. One of the most effective methods for achieving this control is assembly of the optical moieties into chiral nanostructures. Lipopeptide self-assemblies have been extensively employed as soft templates to organize composites into low-dimensional superstructures due to their rigidity and ease of functionalization.

Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance.

Quinolone antimicrobials are widely used in clinical medicine and are the only current class of agents that directly inhibit bacterial DNA synthesis. Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA-enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity. Resistance has emerged with clinical use of these agents and is common in some bacterial pathogens.