Engineering Whole-Cell Biosensors for Enhanced Detection of Environmental Antibiotics Using a Synthetic Biology Approach.

Bacterial Two component systems have evolved with many intricate sensory apparatuses for external stimuli like light, temperature, oxygen, pH and chemical compounds. Recent studies have shown the potential of two-component regulatory systems (TCSs) of bacteria in creating synthetic regulatory circuits for several applications. Antimicrobial resistance is increasing globally in both developing and developed countries and it is one of the foremost global threats to public health. The resistance level to a broad spectrum of antibiotics is rising every year by 5-10%. In this context, TCSs controlling microbial physiology at the transcriptional level could be an appropriate candidate for monitoring the antibiotics present in the environment. This review provided a wide opportunity to gain knowledge about the TCSs available in diverse species to sense the antibiotics. Further, this review explored the EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) based biosensors to repurpose the sensing modules from the microbial TCSs using the synthetic biology approach.

Exploring quinoxaline derivatives: An overview of a new approach to combat antimicrobial resistance.

Antimicrobial resistance (AMR) has emerged as a long-standing global issue ever since the introduction of penicillin, the first antibiotic. Scientists are constantly working to develop innovative antibiotics that are more effective and superior. Unfortunately, the misuse of antibiotics has resulted in their declining effectiveness over the years. By 2050, it is projected that approximately 10 million lives could be lost annually due to antibiotic resistance. Gaining insight into the mechanisms behind the development and transmission of AMR in well-known bacteria including Escherichia coli, Bacillus pumilus, Enterobacter aerogenes, Salmonella typhimurium, and the gut microbiota is crucial for researchers. Environmental contamination in third world and developing countries also plays a significant role in the increase of AMR. Despite the availability of numerous recognized antibiotics to combat bacterial infections, their effectiveness is diminishing due to the growing problem of AMR. The overuse of antibiotics has led to an increase in resistance rates and negative impacts on global health. This highlights the importance of implementing strong antimicrobial stewardship and improving global monitoring, as emphasized by the World Health Organization (WHO) and other organizations. In the face of these obstacles, quinoxaline derivatives have emerged as promising candidates. They are characterized by their remarkable efficacy against a broad spectrum of harmful bacteria, including strains that are resistant to multiple drugs. These compounds are known for their strong structural stability and adaptability, making them a promising and creative solution to the AMR crisis. This review aims to assess the effectiveness of quinoxaline derivatives in treating drug-resistant infections, with the goal of making a meaningful contribution to the global fight against AMR.

Optical biosensors for environmental monitoring: Recent advances and future perspectives in bacterial detection.

The environmental contamination due to bacterial proliferation vs their identification is the major deciding factor in the spread of diseases leading to pandemics. The advent of drug-resistant pathogenic contaminants in our environment has further added to the load of complications associated with their diagnosis and treatment. Obstructing the spread of such infections, prioritizes the expansion of sensor-based diagnostics, effectuating, a sturdy detection of disease-causing microbes, contaminating our surroundings in shortest possible time, with minimal expenditure. Among many sensors known, optical biosensors promote the recognition of pathogens befouling the environment through a comparatively intuitive, brisk, portable, multitudinous, and thrifty approach. This article reviews the recent progresses in optical biosensor-based systems for effective environmental monitoring. The technical and methodological perspectives of fundamental optical-sensing platforms are reviewed, combined with the pros and cons of every procedure. Eventually, the obstacles lying in the path of development of an effective optical biosensor device for bio-monitoring and its future perspectives are highlighted in the present work.

Bacteriophage Therapy to Reduce Colonization of Campylobacter jejuni in Broiler Chickens before Slaughter.

Campylobacteriosis is the most commonly reported gastrointestinal disease in humans. Campybacter jejuni is the main cause of the infection, and bacterial colonization in broiler chickens is widespread and difficult to prevent, leading to high risk of occurrence in broiler meat. Phage therapy represents an alternative strategy to control Campylobacter in poultry. The aim of this work was to assess the efficacy of two field-isolated bacteriophages against experimental infections with an anti-microbial resistant (AMR) Campylobacter jejuni strain. A two-step phage application was tested according to a specific combination between chickens' rearing time and specific multiplicities of infections (MOIs), in order to reduce the Campylobacter load in the animals at slaughtering and to limit the development of phage-resistant mutants. In particular, 75 broilers were divided into three groups (A, B and C), and phages were administered to animals of groups B and C at day 38 (Φ 16-izsam) and 39 (Φ 7-izsam) at MOI 0.1 (group B) and 1 (group C). All broilers were euthanized at day 40, and Campylobacter jejuni was enumerated in cecal contents. Reductions in Campylobacter counts were statistically significant in both group B (1 log10 colony forming units (cfu)/gram (gr)) and group C (2 log10 cfu/gr), compared to the control group. Our findings provide evidence about the ability of phage therapy to reduce the Campylobacter load in poultry before slaughtering, also associated with anti-microbial resistance pattern.

Host-directed Therapy: A New Arsenal to Come.

The emergence of drug-resistant strains among the variety of pathogens worsens the situation in today's scenario. In such a situation, a very heavy demand for developing the new antibiotics has arisen, but unfortunately, very limited success has been achieved in this arena till now. Infectious diseases usually make their impression in the form of severe pathology. Intracellular pathogens use the host's cell machinery for their survival. They alter the gene expression of several host's pathways and endorse to shut down the cell's innate defense pathway like apoptosis and autophagy. Intracellular pathogens are co-evolved with hosts and have a striking ability to manipulate the host's factors. They also mimic the host molecules and secrete them to prevent the host's proper immune response against them for their survival. Intracellular pathogens in chronic diseases create excessive inflammation. This excessive inflammation manifests in pathology. Host directed therapy could be alternative medicine in this situation; it targets the host factors, and abrogates the replication and persistence of pathogens inside the cell. It also provokes the anti-microbial immune response against the pathogen and reduces the exacerbation by enhancing the healing process to the site of pathology. HDT targets the host's factor involved in a certain pathway that ultimately targets the pathogen life cycle and helps in eradication of the pathogen. In such a scenario, HDT could also play a significant role in the treatment of drugsensitive as well with drug resistance strains because it targets the host's factors, which favors the pathogen survival inside the cell.

Recent advances in the development of ß-lactamase inhibitors.

ß-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The ß-lactam resistance in Gram-negative bacteria is due to the production of ß-lactamases, including extended-spectrum ß-lactamases, metallo-ß-lactamases, and carbapenem-hydrolyzing class D ß-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with ß-lactamase inhibitors (BLI). Here we review the medically relevant ß-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.

Rapid Detection of Proliferative Bacteria by Electrical Stimulation.

Detecting live bacteria is an important task for antimicrobial susceptibility testing (AST) in the medical sector and for quality-monitoring in biological industries. Current methods for live-bacteria detection suffer limitations in speed or sensitivity. In a recent paper, we reported that electrical response dynamics in membrane potential enable single-cell rapid detection of live bacteria. The electrical response can be observed within a minute after electrical stimulation. Thus, it has potential in accelerating AST and the monitoring of biological samples. This method also enables experiments for biophysical and microbiological investigations into bacterial electrophysiology. With the hope that more researchers, scientists and engineers will use electrical stimulation for their assays, here we detail each step of the electrical stimulation experiment.