Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides.

The increasing rates of resistance among bacteria and to a lesser extent fungi have resulted in an urgent need to find new molecules that hold therapeutic promise against multidrug-resistant strains. Antimicrobial peptides have proven very effective against a variety of multidrug-resistant bacteria. Additionally, the low levels of resistance reported towards these molecules are an attractive feature for antimicrobial drug development. Here we summarise information on diverse peptide libraries used to discover or to optimize antimicrobial peptides. Chemical synthesized peptide libraries, for example split and mix method, tea bag method, multi-pin method and cellulose spot method are discussed. In addition biological peptide library screening methods are summarized, like phage display, bacterial display, mRNA-display and ribosomal display. A few examples are given for small peptide libraries, which almost exclusively follow a rational design of peptides of interest rather than a combinatorial approach

Is There a Connection Between Gut Microbiome Dysbiosis Occurring in COVID-19 Patients and Post-COVID-19 Symptoms?

According to WHO, currently 215 countries/areas/territories report a total of more than 176 million confirmed COVID-19 cases and 3.8 million deaths (June 18, 2021). SARS-CoV-2, the causative agent of COVID-19, does not impact only the respiratory system but also the various organs in the body. It can directly or indirectly affect the pulmonary system, cardiovascular system (including heart failure), renal system (including kidney failure), hepatic system (including liver failure), gastrointestinal system, nervous system, and/or various systems, leading to shock and multi-organ failure (Zaim et al., 2020). In consequence, comorbidity in these systems leads to a higher risk for a severe disease progression

A short artificial antimicrobial peptide shows potential to prevent or treat bone infections.

Infection of bone is a severe complication due to the variety of bacteria causing it, their resistance against classical antibiotics, the formation of a biofilm and the difficulty to eradicate it. Antimicrobial peptides (AMPs) are naturally occurring peptides and promising candidates for treatment of joint infections. This study aimed to analyze the effect of short artificial peptides derived from an optimized library regarding (1) antimicrobial effect on different bacterial species, (2) efficacy on biofilms, and (3) effect on osteoblast‑like cells. Culturing the AMP-modifications with Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus (including clinical isolates of MRSA and MSSA) and Staphylococcus epidermidis identified one candidate that was most effective against all bacteria. This AMP was also able to reduce biofilm as demonstrated by FISH and microcalorimetry. Osteoblast viability and differentiation were not negatively affected by the AMP. A cation concentration comparable to that physiologically occurring in blood had almost no negative effect on AMP activity and even with 10% serum bacterial growth was inhibited. Bacteria internalized into osteoblasts were reduced by the AMP. Taken together the results demonstrate a high antimicrobial activity of the AMP even against bacteria incorporated in a biofilm or internalized into cells without harming human osteoblasts

Proline-Rich Peptides with Improved Antimicrobial Activity against E. coli, K. Pneumoniae, and A. Baumannii.

Proline-rich antimicrobial peptides (PrAMPs) are promising agents to combat multi-drug resistant pathogens due to a high antimicrobial activity, yet low cytotoxicity. A library of derivatives of the PrAMP Bac5(1-17) was synthesized and screened to identify which residues are relevant for its activity. In this way, we discovered that two central motifs -PIRXP- cannot be modified, while residues at N- and C- termini tolerated some variations. We found five Bac5(1-17) derivatives bearing 1-5 substitutions, with an increased number of arginine and/or tryptophan residues, exhibiting improved antimicrobial activity and broader spectrum of activity while retaining low cytotoxicity toward eukaryotic cells. Transcription/translation and bacterial membrane permeabilization assays showed that these new derivatives still retained the ability to strongly inhibit bacterial protein synthesis, but also acquired permeabilizing activity to different degrees. These new Bac5(1-17) derivatives therefore show a dual mode of action which could hinder the selection of bacterial resistance against these molecules

Magnetostructure of MnAs on GaAs revisited

The ferromagnetic to nonferromagnetic (α-β) phase transition in epitaxial MnAs layers on GaAs(100) is studied by x-ray magnetic circular dichroism and x-ray magnetic linear dichroism photoemission electron microscopy in order to elucidate the nature of the controversial nonferromagnetic state of β-MnAs. In the coexistence region of the two phases the β phase shows a clear XMLD signal characteristic of antiferromagnetism. The nature and the possible causes of the elusiveness of this magnetic state are discussed

Vector Meson Photoproduction with an Effective Lagrangian in the Quark Model

A quark model approach to the photoproduction of vector mesons off nucleons is proposed. Its starting point is an effective Lagrangian of the interaction between the vector meson and the quarks inside the baryon, which generates the non-diffractive s- and u- channel resonance contributions. Additional t-channel $\pi^0$ and $\sigma$ exchanges are included for the $\omega$ and $\rho^0$ production respectively to account for the large diffractive behavior in the small $t$ region as suggested by Friman and Soyeur. The numerical results are presented for the $\omega$ and $\rho$ productions in four isospin channels with the same set of parameters, and they are in good agreement with the available data not only in $\omega$ and $\rho^0$ productions but also in the charged $\rho$ productions where the additional t-channel $\sigma$ exchange does not contribute so that it provides an important test to this approach. The investigation is also extended to the $\phi$ photoproduction, and the initial results show that the non-diffractive behavior of the $\phi$ productions in the large $t$ region can be described by the s- and u- channel contributions with significantly smaller coupling constants, which is consistent with the findings in the similar studies in the QHD framework. The numerical investigation has also shown that polarization observables are essential for identifying so-called "missing resonances".Comment: 36 pages, 10 PS figures, extended version of nucl-th/9711061 and nucl-th/9803021, submitted to PR

Pore-scale Modeling of Viscous Flow and Induced Forces in Dense Sphere Packings

We propose a method for effectively upscaling incompressible viscous flow in large random polydispersed sphere packings: the emphasis of this method is on the determination of the forces applied on the solid particles by the fluid. Pore bodies and their connections are defined locally through a regular Delaunay triangulation of the packings. Viscous flow equations are upscaled at the pore level, and approximated with a finite volume numerical scheme. We compare numerical simulations of the proposed method to detailed finite element (FEM) simulations of the Stokes equations for assemblies of 8 to 200 spheres. A good agreement is found both in terms of forces exerted on the solid particles and effective permeability coefficients

Overview of mathematical approaches used to model bacterial chemotaxis II: bacterial populations

We review the application of mathematical modeling to understanding the behavior of populations of chemotactic bacteria. The application of continuum mathematical models, in particular generalized Keller–Segel models, is discussed along with attempts to incorporate the microscale (individual) behavior on the macroscale, modeling the interaction between different species of bacteria, the interaction of bacteria with their environment, and methods used to obtain experimentally verified parameter values. We allude briefly to the role of modeling pattern formation in understanding collective behavior within bacterial populations. Various aspects of each model are discussed and areas for possible future research are postulated

Analysis of low Reynolds number flow around a heated circular cylinder

The objective of this study is to investigate the forced convection from and the flow around a heated cylinder. Experimental and computational results are presented for laminar flow around a heated circular cylinder with a diameter of 10 mm. The experiments were carried out using Particle Image Velocimetry (PIV) in a wind tunnel, and numerical simulations using an in-house code and a commercial software package, FLUENT. This paper pre-sents comparisons for vorticity and temperature contours in the wake of the cylinder. Experimental and computa-tional results are compared with those available in the literature for heated and unheated cylinders. An equation is suggested for a temperature-dependent coefficient defining a reference temperature to be used in place of the con-stant used in other studies. An attempt is also made to correct differences between average cylinder surface tem-perature and measured interior temperature of the cylinder