Rational Design of ROS-Responsive, ROS-Scavenging, and Bacterial Membrane-Disrupting Self-Antibacterial...

Area of Science:

• Materials Science
• Biotechnology
• Medicinal Chemistry

Background:

• Antibiotic resistance is a growing global health crisis, necessitating novel therapeutic approaches.
• Self-antibacterial supramolecular gels offer a promising strategy by disrupting bacterial membranes.

Purpose of the Study:

• To design and synthesize reactive oxygen species (ROS)-responsive low-molecular-weight gelators (LMWGs) for self-antibacterial supramolecular gels.
• To evaluate the antibacterial efficacy and mechanism of action of these novel gels against drug-resistant bacteria.

Main Methods:

• Synthesis of ROS-responsive LMWGs incorporating antibacterial synthons and a thioacetal linker.
• Characterization of gel properties, including rheology, ROS responsiveness, and drug release.
• Assessment of antibacterial activity against *Staphylococcus aureus* and *Escherichia coli*, including MRSA, via various assays.
• Investigation of the antibacterial mechanism, including bacterial membrane disruption and intracellular component release.

Main Results:

• The synthesized LMWGs formed ROS-responsive supramolecular gels.
• The blank gel demonstrated potent antibacterial and bactericidal activity comparable to antibiotic-loaded gels.
• The gel effectively disrupted bacterial membranes, leading to cell death and intracellular DNA release.
• Significant efficacy was observed against methicillin-resistant *Staphylococcus aureus* (MRSA).

Conclusions:

• Rational design of LMWGs for targeted membrane disruption is a viable strategy for developing self-antibacterial supramolecular gels.
• These novel gels present an innovative platform for combating drug-resistant bacterial infections.
• The findings pave the way for new treatments against challenging bacterial pathogens.