The Enemy of My Enemy Is My Friend: Bacteriophages For The Control of Drug-Resistant Bacteria In Biofilms

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About this Research Topic

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Background

The increase and the rapid spread of drug-resistant bacteria represent one of the greatest challenges faced by modern medicine. In 2019, antimicrobial resistance had been listed by the WHO among the ten major threats to global health. Therefore, the research and the development of new effective antimicrobial strategies are of critical importance.

Around 80% of infections are due to biofilm-embedded bacteria, which represent a further tremendous challenge for modern medicine since these biofilms are difficult to eradicate with the currently available antimicrobial therapy.
Formation of biofilm is a survival strategy deployed by microorganisms to adapt to hostile environmental conditions: microbial cells attach on biotic or abiotic surfaces and stick to each other via a self-produced extracellular matrix that shields them from both therapeutic antibiotics and the host immune system. Microbial cells within biofilms
represent a metabolically heterogeneous population which has been shown to include persister cells. These bacterial cells, which are tolerant to the most known antibiotics, might be responsible for the recalcitrance of infections once the antibiotic selective pressure is reduced.

While in vitro investigations have shown that very high concentration of antibiotics (up to 1000 times more than the MIC of planktonic bacteria) can eradicate biofilms, such high concentrations are not recommended in routine clinical practices making a prolonged course of combined antibiotic therapy the only possible treatment regime. However, critically undermining this therapeutic option, the constant presence of antibiotics at sub-therapeutic concentrations can spur bacteria in biofilm to develop antibiotic-resistance. Antibiotic-resistant sessile cells are,
therefore, a key challenge for the treatment of biofilm-associated infections.

Among the many innovative antimicrobial strategies currently under evaluation, therapies based on the use of bacteriophages (phages) have been regarded among the most promising options. Phage therapy, based on the application of viruses able to selectively kill bacteria (and nothuman cells), is reemerging as an antimicrobial therapeutic choice in both clinical and scientific fields, particularly when bacteria are refractory to conventional antibiotic treatments. An ever-growing number of case reports have recently described the use of phages on their own or in combination with antibiotics for the treatment of chronic infections.

The aim of this Research Topic is to provide the readers with an updated and comprehensive overview of the use of phages as therapeutics for the prevention and the treatment of biofilm-associated infections, in particular of those due to antibiotic-resistant bacteria. Drug delivery systems for the release of phages at the site of infection will be of interest as well as reports dealing with the immune response to phage therapy. We encourage the submission of articles reviewing the current state-of-the-art or providing novel scientific insights aiming to improve the
management of biofilm-associated infections through phage therapy.

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Keywords: Bacterial biofilm, bacteriophages, chronic infections, antimicrobial therapy

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