Pooja Gulati

During the past few decades, a significant increase in antibiotic resistance has been encountered worldwide, posing a serious threat to human health. The inadvertent use of antibiotics in human/vet...

The human gut microbiome is critical in promoting human health in many aspects, like facilitating nutrient absorption, digestion, immune system regulation, and protecting against pathogens. Gut microbiota dysbiosis is associated with the pathogenesis of several infectious diseases. In this context, a combination of prebiotics and probiotics as synbiotics is emerging as a popular approach for managing immune and gastrointestinal health. Synbiotics have exhibited considerable potency in restoring eubiosis via modulating the gut microbiome. The dietary supplementation of synbiotics has shown promising results in treating infectious diseases like hepatitis, gastroenteritis, dental caries, and sepsis. Synbiotics antagonise pathogens by maintaining gut microbiota homeostasis, competing with pathogenic microorganisms for adhesion and nutrition, producing antimicrobial compounds, and stimulating immunomodulatory cells in vivo. The present article has been conceptualised to understand the potential of synbiotics as an alternative or adjunct to antibiotics in managing infectious diseases. Furthermore, it elaborates on the different formulations of synbiotics available for clinical use and their mode of action. Challenges associated and recent approaches to improve the efficacy of these therapeutics have also been addressed.

In the present study, nutraceutical citrulline was produced using immobilization of permeabilized whole cells of Pseudomonas furukawaii, an efficient producer of ADI. Since ADI is intracellularly localized, various additives such as SDS, Triton X-100, and EDTA were used to permeabilize the cell to improve substrate accessibility and ADI activity. The maximum ADI activity was observed with 0.25 mg mL⁻¹ biomass concentration treated with 0.5 mmol L⁻¹ EDTA for 15 min using OFAT approach. Optimization of permeabilization conditions of P. furukawaii cells using novel neural networks and particle swarm optimization (PSO-NN) led to maximum ADI activity with 0.10 mmol L⁻¹ EDTA and 0.30 mg mL⁻¹ biomass. Further, the morphological characterization of immobilized cells was assessed by FESEM and FTIR. An optimal citrulline production of 1.19 mmol L⁻¹ was achieved at 2.5% sodium alginate with 20 mmol L⁻¹ arginine at 38°C, and 180 min of incubation. The immobilized cells retained 90.3% productivity after seven reuse cycles. Thus, the formulated immobilized whole-cell biocatalyst, with higher stability offers cost-effective methods of citrulline production.

Nanocarrier-based immobilization has created new avenues for enhancing the biophysical properties of enzymes. Nanomatrices such as magnetite nanoparticles (MNPs), chitin, and chitosan with large surface areas and tunable morphology have been developed to circumvent the bottlenecks of free enzymes. The present study used MNPs to immobilize the enzyme arginine deiminase (ADI) for improved morphological control, recovery, operational stability, and easy recyclability. Hybrid magnetic arginine deiminase cross-linked enzyme aggregate (mADI-CLEA) was developed for the first time by co-aggregating ADI with magnetite nanocomposites, followed by its cross-linkage with glutaraldehyde. Structural analysis by DLS/ZETA, SEM, and FT-IR revealed their highly stable and robust nature. The resulting mADI-CLEA exhibited higher pH resistivity and thermostability than ADI-CLEA. Reusability and storage stability assay indicated that mADI-CLEA maintained more than 60% residual activity even after seven batch cycles and was stable for more than 70 days. These hybrid magnetic aggregates of ADI offer an economical and stable alternative for biomedical applications of ADI.

Fungal infections are one of the major causes of fatalities worldwide, causing an estimated 1.5 million deaths annually. Over the past few decades, the incidences of fungal infection have risen with the increase in the cases of immunocompromised patients. However, the impact of fungal diseases on public health is often underestimated. These infections are predominantly caused by the Aspergillus, Candida, and Cryptococcus species. Current therapeutic approaches to treat such fungal infections are limited to five distinct classes of antifungal drugs, viz. polyenes, echinocandins, azoles, pyrimidine analogs, and allylamines. Moreover, a few synthetic molecules are also used as fungicidal agents. Despite the current antifungal armamentarium, the burden of fungal infection is exacerbated by the emergence of drug resistance, host toxicity, and negative interactions with other drugs. The paucity of new antifungal drugs has further complicated the treatment of fungal infections. These limitations provide a rationale for developing novel antifungals preferably with new mechanisms and molecular targets. This chapter thus summarizes the currently used antifungal drugs, their effective combinations, and the challenges inherent to the development of new antifungal drugs. The chapter also addresses strategies to bolster the antifungal pipeline involving emerging new targets for better management of fungal infections.