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Conjugated oligoelectrolytes (COEs) are an emerging class of amphiphilic antimicrobial compounds with a modular molecular framework suitable for simple chemical derivatization. Here, a series of COE derivatives with a stilbene‐conjugated segment and triphenylphosphonium (TPP) pendant groups was designed and synthesized to understand how lipophilic cationic groups impact antimicrobial activity. In vitro evaluations against ESKAPE pathogens showed broad‐spectrum activity towards multi‐drug resistant (MDR) bacteria and mycobacteria, with TPP groups enhancing antimicrobial activity towards clinically relevant Gram‐negative strains compared to their ammonium analogues. We studied the interactions of DM6P, the most active TPP‐COE compound, with various membrane assays. Treatment of bacterial cells with DM6P showed enhanced permeability of cell membranes without inducing the development of significant bacterial resistance. Moreover, DM6P eliminated 99.99 % of methicillin‐resistant Staphyloccocus aureus (MRSA) in an in vivo wound model. These results represent a promising chemical strategy for increasing the activity spectrum of membrane‐active COE antibiotics to tackle challenging drug‐resistant targets. [ABSTRACT FROM AUTHOR]

In previous studies we have described the therapeutic action of luminescent dinuclear ruthenium(II) complexes based on the tetrapyridylphenazine, tpphz, bridging ligand on pathogenic strains of Escherichia coli and Enterococcus faecalis. Herein, the antimicrobial activity of the complex against pernicious Gram‐negative ESKAPE pathogenic strains of Acinetobacter baumannii (AB12, AB16, AB184 and AB210) and Pseudomonas aeruginosa (PA2017, PA_ 007_ IMP and PA_ 004_ CRCN) are reported. Estimated minimum inhibitory concentrations and minimum bactericidal concentrations for the complexes revealed the complex shows potent activity against all A. baumannii strains, in both glucose defined minimal media and standard nutrient rich Mueller‐Hinton‐II. Although the activity was lower in P. aureginosa, a moderately high potency was observed and retained in carbapenem‐resistant strains. Optical microscopy showed that the compound is rapidly internalized by A. baumannii. As previous reports had revealed the complex exhibited no toxicity in Galleria Mellonella up to concentrations of 80 mg/kg, the ability to clear pathogenic infection within this model was explored. The pathogenic concentrations to the larvae for each bacterium were determined to be≥105 for AB184 and≥103 CFU/mL for PA2017. It was found a single dose of the compound totally cleared a pathogenic A. baumannii infection from all treated G. mellonella within 96 h. Uniquely, in these conditions thanks to the imaging properties of the complex the clearance of the bacteria within the hemolymph of G. mellonella could be directly visualized through both optical and transmission electron microscopy. [ABSTRACT FROM AUTHOR]

Field‐effect transistor (FET) biosensors based on hybrid nanostructures present unique advantages of high sensitivity, small size, excellent dynamic range, and compatibility with integrated circuits. In this work, the fabrication of highly sensitive and selective hybrid MoS2/TiO2 nanostructure‐based FET is demonstrated for the detection of Gram‐positive bacteria. The fabricated FET biosensors are efficiently capable of discriminating between Gram‐positive and Gram‐negative bacteria with a limit of detection 50 cfu mL−1. The biosensor exhibits a high sensitivity of 49.47 ± 1.7% for Staphylococcus aureus among eight different bacteria at a concentration of 102 cfu mL−1. The real time detection of bacteria with a response time of 22.19 s is achieved at concentrations as low as 50–100 cfu mL−1, suggesting rapid and low concentration detection of selective bacteria. The FET biosensor is also able to quantify bacteria in the physiological conditions as well as discriminate between live and dead bacteria. The unique hybrid nanostructure based FET with desirable biosensing properties presents the potential to screen the pathogenic bacteria. Live/dead monitoring of bacteria may help in deciding the course and dosage of the antibiotic treatment. [ABSTRACT FROM AUTHOR]

Antibiotic resistant pathogens are a modern threat to the human health. As a worldwide spreading problem, there is an urgency for new strategies to minimize antibiotic resistance, particularly the super‐resistant strains. Here, the efficient design of carbohydrate‐coated silica nanoparticles is reported which specifically target Gram‐negative bacteria cells. The system is functionalized with gluconamide moieties and demonstrates increased binding ability to the bacterial membrane, enabling controlled drug delivery onto the pathogen wall. In addition, the high stability of the nanoparticles in biological media and the lack of non‐specific protein adhesion are engendered by such functionalization, which also demonstrates low cytotoxicity and hemolytic activity prevention. Local interaction between nanoparticles and the bacterium membrane is experimentally accessed at the biomolecular level unveiling a short‐range chemical connection. Atomistic molecular dynamics simulations depict the rapid penetration of gluconamide in the lipopolysaccharide region of the bacterial outer membrane, corroborating the experimental findings. Thus, this novel outer membrane‐targeting platform provides a new strategy to reduce drug intake and, hence, minimize bacterial resistance. [ABSTRACT FROM AUTHOR]