Phage therapy: awakening a sleeping giant

Abstract

Correspondence: Laurent Debarbieux (laurent.debarbieux@pasteur.fr)For a century, bacterial viruses called bacteriophages have been exploited as natural antibacterial agents. However, their medicinal potential has not yet been exploited due to readily available and effective antibiotics. After years of extensive use, both properly and improperly, antibiotic-resistant bacteria are becoming more prominent and represent a worldwide public health threat. Most importantly, new antibiotics are not progressing at the same rate as the emergence of resistance. The therapeutic modality of bacteriophages, called phage therapy, offers a clinical option to combat bacteria associated with diseases. Here, we discuss traditional phage therapy approaches, as well as how synthetic biology has allowed for the creation of designer phages for new clinical applications. To implement these technologies, several key aspects and challenges still need to be addressed, such as narrow spectrum, safety, and bacterial resistance. We will summarize our current understanding of how phage treatment elicits mammalian host immune responses, as well bacterial phage resistance development, and the potential impact each will have on phage therapy effectiveness. We conclude by discussing the need for a paradigm shift on how phage therapy strategies are developed.

Human neutrophil response to Pseudomonas bacteriophages

“…Moreover, phages has been proposed as a human antibacterial therapy, namely phage therapy, to address the rise of multidrug resistant infections (14,15). The mechanism by which phages exert their therapeutic action has generally been considered to be via their capacity to lyse bacterial cells.…”

Isolation and characterization of bacteriophages that infect Citrobacter rodentium, a model pathogen for investigating human intestinal diseases

“…Moreover, virulent phages similar to CrRp3 and CrRp10 are being re-investigated as potential antimicrobial agents to both combat bacterial diseases and the dissemination of MDR bacteria (12). Because mice are resistant to EPEC and EHEC infections, C. rodentium is widely used as an in vivo model system for several important human gastrointestinal diseases (44,45).…”

“…As both obligate parasites and vectors of horizontal gene transfer, a better understanding of phage strain diversification and how viral diversity might impact bacterial diversity and populations is required. Furthermore, there is renewed interest in the use of phages to eliminate or modulate bacterial population, namely phage therapy, partly due to their specificity for host bacterial species and ability to kill MDR pathogens (12,13).…”

Advanced therapies push regulatory boundaries

“…The underlying problem is that compared with antibiotics, there are currently no phage products that have satisfied established regulatory framework in Europe or the United States. This issue has been acknowledged by the EMA, which called for more clinical trials before contemplating any adaptation of the regulatory framework . To some extent, this is a challenge for most if not all emerging therapies, for even if the broad framework is adequate, research is advancing rapidly.…”

“…Regulatory frameworks for advanced therapies EMBO reports contemplating any adaptation of the regulatory framework [7]. To some extent, this is a challenge for most if not all emerging therapies, for even if the broad framework is adequate, research is advancing rapidly.…”