The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics.

The outbreak of the coronavirus disease (COVID-19) pandemic caused by the novel coronavirus (SARS-CoV-2) has been declared an international public health crisis. It is essential to develop diagnostic tests that can quickly identify infected individuals to limit the spread of the virus and assign treatment options. Herein, we report a proof-of-concept label-free electrochemical immunoassay for the rapid detection of SARS-CoV-2 virus via the spike surface protein. The assay consists of a graphene working electrode functionalized with anti-spike antibodies. The concept of the immunosensor is to detect the signal perturbation obtained from ferri/ferrocyanide measurements after binding of the antigen during 45 min of incubation with a sample. The absolute change in the [Fe(CN)₆]₃−/⁴⁻ current upon increasing antigen concentrations on the immunosensor surface was used to determine the detection range of the spike protein. The sensor was able to detect a specific signal above 260 nM (20 µg/mL) of subunit 1 of recombinant spike protein. Additionally, it was able to detect SARS-CoV-2 at a concentration of 5.5 × 10⁵ PFU/mL, which is within the physiologically relevant concentration range. The novel immunosensor has a significantly faster analysis time than the standard qPCR and is operated by a portable device which can enable on-site diagnosis of infection.

The constant emergence of new bacterial strains that resist the effectiveness of marketed antimicrobials has led to an urgent demand for and intensive research on new classes of compounds to combat bacterial infections. Antimicrobial peptoids comprise one group of potential candidates for antimicrobial drug development. The present study highlights a library of 22 cationic amphipathic peptoids designed to target bacteria. All the peptoids share an overall net charge of +4 and are 8 to 9 residues long; however, the hydrophobicity and charge distribution along the abiotic backbone varied, thus allowing an examination of the structure-activity relationship within the library. In addition, the toxicity profiles of all peptoids were assessed in human red blood cells (hRBCs) and HeLa cells, revealing the low toxicity exerted by the majority of the peptoids. The structural optimization also identified two peptoid candidates, 3 and 4, with high selectivity ratios of 4 to 32 and 8 to 64, respectively, and a concentration-dependent bactericidal mode of action against Gram-negative Escherichia coli .

Peptoids are an alternative approach to antimicrobial peptides that offer higher stability towards enzymatic degradation. It is essential when developing new types of peptoids, that mimic the function of antimicrobial peptides, to understand their mechanism of action. Few studies on the specific mechanism of action of antimicrobial peptoids have been described in the literature, despite the plethora of studies on the mode of action of antimicrobial peptides. Here, we investigate the mechanism of action of two short cationic peptoids, rich in lysine and tryptophan side chain functionalities. We demonstrate that both peptoids are able to cause loss of viability in E. coli susceptible cells at their MIC (16–32 μg/ml) concentrations. Dye leakage assays demonstrate slow and low membrane permeabilization for peptoid 1, that is still higher for lipid compositions mimicking bacterial membranes than lipid compositions containing Cholesterol. At concentrations of 4 × MIC (64–128 μg/ml), pore formation, leakage of cytoplasmic content and filamentation were the most commonly observed morphological changes seen by SEM in E. coli treated with both peptoids. Flow cytometry data supports the increase of cell size as observed in the quantification analysis from the SEM images and suggests overall decrease of DNA per cell mass over time.

Despite intensive antibiotic treatment,Pseudomonas aeruginosaoften persists in the airways of cystic fibrosis (CF) patients for decades, and can do so without antibiotic resistance development. Using high-throughput screening assays of bacterial survival after treatment with high concentrations of ciprofloxacin, we have determined the prevalence of persisters in a large patient cohort using 460 longitudinal isolates ofP.aeruginosafrom 39 CF patients. Isolates were classed as high persister variants (Hip) if they regrew following antibiotic treatment in at least 75% of the experimental replicates. Strain genomic data, isolate phenotyping, and patient treatment records were integrated in a lineage-based analysis of persister formation and clinical impact. In total, 19% of the isolates were classified as Hip and Hip emergence increased over lineage colonization time within 22 Hip+ patients. Most Hip+ lineages produced multiple Hip isolates, but few Hip+ lineages were dominated by Hip. While we observed no strong signal of adaptive genetic convergence within Hip isolates, they generally emerged in parallel or following the development of ciprofloxacin resistance and slowed growth. Transient lineages were majority Hip-, while strains that persisted over a clinically diagnosed ‘eradication’ period were majority Hip+. Patients received indistinguishable treatment regimens before Hip emergence, but Hip+ patients overall were treated significantly more than Hip- patients, signaling repeated treatment failure. When subjected toin vivo-similar antibiotic dosing, a Hip isolate survived better than a non-Hip in a structured biofilm environment. In sum, the Hip phenotype appears to substantially contribute to long-term establishment of a lineage in the CF lung environment. Our results argue against the existence of a single dominant molecular mechanism underlying bacterial antibiotic persistence. We instead show that many routes, both phenotypic and genetic, are available for persister formation and consequent increases in strain fitness and treatment failure in CF airways.

Our main goal was to investigate if and how using multiple immersive virtual reality (iVR) simulations and their video playback, in a science course, affects student learning over time. We conducted a longitudinal study, in ecological settings, at an undergraduate field-course on three topics in environmental biology. Twenty-eight undergraduates were randomly assigned to either an iVR-interaction group or a video-viewing group. During the field-course, the iVR group interacted with a head-mounted device-based iVR simulation related to each topic (i.e. total three interventions), while the video group watched a pre-recorded video of the respective simulation on a laptop. Cognitive and affective data were collected through the following checkpoints: a pre-test before the first intervention, one topic-specific post-test immediately after each intervention, a final post-test towards the end of the course, and a longitudinal post-test deployed approximately 2 months after the course. Through a descriptive analysis, it was found that student performance on the knowledge tests increased considerably over time for the iVR group but remained unchanged for the video group. While no within- or between-group differences were noted for intrinsic motivation and self-efficacy measures, students in the iVR group enjoyed all the simulations, and perceived themselves to benefit from those simulations.