Triple-Acting Antibiotic Agent: Efficacy in Effectively Killing Bacteria Revealed in New Study

New research recently showed a new triple-acting antibiotic agent has managed to break through the biofilm extracellular matrix and take out more than 50 percent of the pathogens in a single shot.

As specified in a Phys.org report, "Persistent lung infections, chronic wounds, and health care-associated infections" are usually much harder to treat compared ot other bacterial infectiont ypes.

This is because they are frequently caused by biofilms, or colonies of microbes, mainly bacteria, that are growing together in a self-generated matrix that shields and isolates them from the outer environment.

The study was led by lecturer Eduardo Torrents from the Department of Genetics, Microbiology, and Statistics of the Faculty of Biology and head of the group of Bacterial Infections: Antimicrobial Therapy of the IBEC or Institute for Bioengineering of Catalonia.

Extracellular Matrix Exacerbating Antibiotic Resistance

The extracellular matrix exacerbates antibiotic resistance, one of the biggest threats to worldwide health, according to the World Health Organization, since killing the bacteria inside the film is up to 1,000 times more difficult.

Biofilm infections are consequently the most essential nonspecific mechanism of antibacterial resistance. Attacking such bacteria using just antibiotics is not enough.

There is a need for mechanisms that are breaking down the extracellular matrix to access and destroy the bacteria inside.

The first author of this research which has achieved this milestone is postdoctoral researcher Nuria Blanco-Cabra, from the group led by Eduard Torrents at the UB and IBEC. This work was performed together with researchers from CIDETEC in Basque County.

Triple-Acting

The study published in npj Biofilms and Microbiomes, focused on the bacteria known as Pseudomonas areuginosa, a pathogen that's frequently growing in biofilms in the lungs of patients who have cystic fibrosis or chronic obstructive pulmonary disease (COPD), leading to persistent infections.

Torrents also explained that they grew biofilm cultures in vitro, employing an approach that's similar to the manner in which they exist and grow in nature.

In the clinical background, such infections are typically treated with an antibiotic known as tobramycin. Nonetheless, its efficacy is limited by its inability to infiltrate the film.

This occurs since tobramycin, which is positively charged, is neutralized by the extracellular matrix, with a negative charge.

'DNase I'

The study investigators loaded the antibiotic into negatively charged nanoparticle carriers. This then could neutralize the positive charge before the drug reached the biofilm, enabling it to break the extracellular matrix and destroy the microbes inside.

What is more essential, these carriers, built by dextran-based single-chain nanoparticles, were able to transport up to 40 percent of the weight of the antibiotic.

Many of the previously investigated nanotransporters have only been able to retain a small load of the target compound, which has prevented their clinical employment. The team was able to overcome such an obstacle.

The antibiotic-loaded nanocarriers were coated in an enzyme as well, which is called DNase I. One of the compounds holding bacteria biofilms together is known as "structural DNA found throughout the extracellular matrix, according to the IBEC report.

Essentially, this DNase I can break down the glue that causes the matrix to loosen, enabling the antibiotic to infiltrate the biofilm even further.

Related information about antibiotic resistance is shown on 60 Minutes's YouTube video below:

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