Ultrasonic Microbubbles: A Novel Approach to Eradicating Antibiotic-Tolerant Bacterial Biofilms

Chronic infections associated with bacterial biofilms pose a significant challenge in healthcare, rendering many antibiotics ineffective. While antimicrobial resistance is a well-recognised global threat, antibiotic tolerance due to biofilms is an equally concerning issue.

Researchers are now exploring innovative approaches, such as ultrasonic microbubble therapy, to combat these persistent infections. Bacterial biofilms are complex communities encased in a self-produced extracellular matrix. This matrix acts as a protective barrier, preventing antibiotics from reaching the bacteria within.

Ultrasound, a well-established medical imaging technique, is now being repurposed to combat biofilm-associated infections. By combining ultrasound with specially engineered phase-shift microbubbles and enhanced antibiotics, researchers aim to penetrate the biofilm matrix and target persister cells.

The engineering behind ultrasonic microbubble therapy relies on precisely manipulating high-frequency sound waves and microscopic gas bubbles. Initially, in a liquid state, phase-shift microbubbles transform into gas when exposed to specific ultrasound pressures. The microbubbles expand and contract as the ultrasound waves oscillate, creating transient pores in the biofilm matrix. This allows antibiotic molecules to penetrate deep into the biofilm.

To further enhance the effectiveness of the antibiotics, researchers incorporate adjuvants that enable the drugs to latch onto persister cells. These adjuvants act as “pins” that insert into the bacterial membrane, facilitating drug uptake even in metabolically inactive cells. Combining ultrasound, phase-shift microbubbles, and enhanced antibiotics creates a targeted approach to eradicating biofilm-associated infections.

Preclinical studies have shown promising results for ultrasonic microbubble therapy. In mouse models of chronic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA), the treatment reduced bacterial levels by 99% compared to standard care. Researchers have also successfully used the technique to treat biofilm-associated infections in bladder and urinary tract organoid models.

However, translating this therapy to human patients presents a few important safety considerations. The microbubbles, now modified with attached drug molecules, may be considered a new drug entity by regulatory agencies, and there are concerns about the potential for dislodged bacteria to cause systemic infections. However, researchers argue that this risk is minimal compared to current surgical debridement practices.