Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia

Abstract

Southeast Asia (SEA) can be considered a hotspot of antimicrobial resistance (AMR) worldwide. As recent surveillance efforts in the region reported the emergence of multidrug-resistant (MDR) pathogens, the pursuit of therapeutic alternatives against AMR becomes a matter of utmost importance. Phage therapy, or the use of bacterial viruses called bacteriophages to kill bacterial pathogens, is among the standout therapeutic prospects. This narrative review highlights the current understanding of phages and strategies for a phage revolution in SEA. We define phage revolution as the radical use of phage therapy in infectious disease treatment against MDR infections, considering the scientific and regulatory standpoints of the region. We present a three-phase strategy to encourage a phage revolution in the SEA clinical setting, which involves: (1) enhancing phage discovery and characterization efforts, (2) creating and implementing laboratory protocols and clinical guidelines for the evaluation of phage activity, and (3) adapting regulatory standards for therapeutic phage formulations. We hope that this review will open avenues for scientific and policy-based discussions on phage therapy in SEA and eventually lead the way to its fullest potential in countering the threat of MDR pathogens in the region and worldwide.

The applications of animal models in phage therapy: An update

“…The viral genome replicates with the host DNA in lysogenicity, either as a free plasmid-like state or after integration into the bacterial chromosome. 137 A more serious issue is that bacteriophages in the lysogenic state can transmit toxins and antibiotic resistance genes to bacteria. Unlike protein drugs, whose activity and purity can be determined using specific antibody titers, the composition of phage therapy preparations are more complex, containing both proteins and nucleic acids.…”

Limitations of Phage Therapy and Corresponding Optimization Strategies: A Review

“…The lysogenic phenomenon consist in the fact that some lysogenic phages cannot lyse the host bacteria and inhibit the lytic effect of other phages on their host bacteria after integration with the host bacteria. In lysogenicity, the viral genome replicates with the host DNA, either in a free plasmid-like state or after integration into the bacterial chromosome [ 13 ]. In addition, a more important problem is that bacteriophages in the lysogenic state can also transmit toxins and antibiotic resistance genes to bacteria.…”

“…The CRISPR–Cas system works in at least two stages: the adaptation stage, in which cells acquire new spacer sequences from exogenous DNA, and the interference phase, in which recently obtained spacers are used to target and cleave invasive nucleic acids. The CRISPR–Cas system participates in the continuous evolution of bacteriophages and bacteria by adding or deleting gaps in host cells and mutations or deletions in phage genomes [ 13 , 69 ].…”

“…However, in recent years, the relentless rise in antibiotic resistance has ignited a renewed interest in PT and provided a new impetus for research on bacteriophage-based bacterial infection solutions. The Southeast Asia region has embarked on a phage revolution, paving the way for phage therapy and related policies and addressing the threat posed by multidrug-resistant pathogens in the region and around the world [ 13 ].…”

Isolation and phenotypic characterization of bacteriophage SA14 with lytic- and anti-biofilm activity against multidrug-resistant Enterococcus faecalis

“…Phage therapy has been used for enteric and systemic therapies in nations like Russia, Poland, and Eastern Europe [26]. Georgia's Institute of Bacteriophage, Microbiology, and Virology is an institution for phage therapy [27]. Lately, phage management has gained more attention as a consequence of the increase in the frequency of bacterial multi-, extensively, and pandrug resistance [24].…”