Triggered Release of Bacteriophage K from Agarose/Hyaluronan Hydrogel Matrixes by Staphylococcus aureus Virulence Factors

Abstract

The use of hydrogels as safe, biocompatible materials for wound healing has been widely utilized in recent years. Here, we investigated the use of a composite hydrogel to impart a "trigger" mechanism into an antimicrobial hydrogel system. The system was comprised of a bilayer hydrogel architecture: a lower agarose layer containing the antimicrobial virus Bacteriophage K (ΦK) and an upper layer formed of photo-cross-linkable hyaluronic acid methacrylate (HAMA) which creates the hydrogel trigger. This trigger is sensitive to the enzyme hyaluronidase, an enzyme known to be secreted by the majority of Staphylococcus aureus strains. In the presence of hyaluronidase, HAMA is degraded, releasing ΦK into the surrounding environment which consequently go on to kill surrounding bacteria. Our results show that on incubation with hyaluronidase (purified or from S. aureus), large pores form in HAMA as degradation goes on, which facilitates ΦK release.

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

“…In future different phage fomulations may need to be developed targeting phage release in the appropriate intestinal region perhaps using more specific infection related triggers e.g. enzymes or toxins released by the bacterium causing the infection [95]. …”

Thermally triggered release of the bacteriophage endolysin CHAPK and the bacteriocin lysostaphin for the control of methicillin resistant Staphylococcus aureus (MRSA)

“…Ensuring activity, stability and dosage conditions are correct (especially when considering biological material), is crucial to successful administration in order to maximise the therapeutic benefit and to reduce any potential side effects. The triggered release of a therapeutic agent (small molecule, protein or virus) may rely on a variety of external stimuli in order to release the active cargo, including pH, temperature, ultrasound, magnetism or biomarker signals [24], [25]. Utilising the difference between the healthy and the diseased state may provide certain conditions whereby treatment can be administered in a controlled fashion.…”

Hyaluronic Acid–Modified Porous Silicon Films for the Electrochemical Sensing of Bacterial Hyaluronidase

“…To confirm and quantify the degradation of the synthesized HYAMA by the target enzyme hyal, the breakdown product N ‐acetylglucosamine (NAG) (Figure S5, Supporting Information), was quantified using a modified carbazole assay published by Bean et al in 2014 . The assay is based on the colorimetric method for the quantification of N ‐acetylamino sugars by UV–vis spectroscopy, reported for the first time by Reissig et al in 1955 .…”

“…Interestingly, high levels of hyal are observed just before the exponential growth phase sets in. This enzymatic degradation of HYA‐based polymers by hyal has been exploited in signaling hydrogels and nanocapsules before for sensing high levels of the enzyme that indicate a bacterial infection …”