Enhancing the Stability of Bacteriophages Using Physical, Chemical, and Nano-Based Approaches: A Review

Abstract

Phages are efficient in diagnosing, treating, and preventing various diseases, and as sensing elements in biosensors. Phage display alone has gained attention over the past decade, especially in pharmaceuticals. Bacteriophages have also found importance in research aiming to fight viruses and in the consequent formulation of antiviral agents and vaccines. All these applications require control over the stability of virions. Phages are considered resistant to various harsh conditions. However, stability-determining parameters are usually the only additional factors in phage-related applications. Phages face instability and activity loss when preserved for extended periods. Sudden environmental changes, including exposure to UV light, temperature, pH, and salt concentration, also lead to a phage titer fall. This review describes various formulations that impart stability to phage stocks, mainly focusing on polymer-based stabilization, encapsulation, lyophilization, and nano-assisted solutions.

Bacteriophage-host interactions in microgravity onboard the International Space Station

“…At the 23-day timepoint, we observed a seven- and four-log decrease in phage titers in microgravity and gravity respectively, a loss much greater than the 1-2 log loss we observed for bacterial titers. Phages are known to lose stability over time without a propagating host [13,14], and this effect appeared larger in microgravity compared to terrestrial incubation.…”

“…Phage saw an overall decrease in viable titer in early time points in microgravity compared to terrestrial incubation but otherwise were more stable than bacteria, except for the 23-day timepoint, where we observed a seven- and four-log fold decrease in phage titers in microgravity and gravity respectively. Phages are known to lose stability over time without a propagating host [13,14], and this effect appeared larger in microgravity compared to terrestrial incubation. In summary, these experiments demonstrate that microgravity presents a challenge to phage and bacterial viability.…”

Characterization of Bacillus thuringiensis bacteriophages: morphogenesis, lytic potentials & inter-simple sequence repeat (ISSR) analysis

“…These results agreed with other researchers since phages have a limited host range with high speci city toward their hosts ( One of the challenges of using Bacillus thuringiensis in biological control is the presence of soil bacteriophages, the bacteriophage-host interaction under certain environmental parameters is considered a limiting factor in biological pest control. Therefore, for successful use of Bt in biocontrol a continuous screening and mapping of Bt phages, along with the external environmental factors such as the pH, temperature, and UV radiation present in the area of application is a must to improve the insecticidal validity (Duyvejonck et al 2021;Wdowiak et al 2022). To develop a successful, and effective stable Bt working dose that withstands the persistent soil phage and other environmental parameters that in uence the phage vitality, replication, and infectivity the soil and environmental parameters are considered.…”

Biophysical Breakthroughs Projected for the Phage Therapy of Bacterial Disease

“…These studies appear to have been conducted without awareness of the points made in the previous paragraph, a condition that continues to the most recent review [65]. Nonetheless, when one averages a very large amount of data presented in [65], the conclusion is drawn that among the sugars tested as drying-stabilizers, trehalose and sucrose, both non-reducing disaccharides, are the most effective. Other sugars tested include two disaccharides, both reducing: maltose (α-linked) and lactose (β-linked).…”

“…Studies in this general direction have been conducted for (1) stabilizing phages for aerosol delivery [60,61], (2) freeze drying, and (3) in-air spray drying [62][63][64][65]. Spray drying is closest to what happens in the environment.…”