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Bacteriophages: Molecular and Virologic Review Study

Majida Hameed Obaida
Saif Jabbar Yasir
Journal of Progressive Medical Sciences, Vol. 1 No. 2 (2025): Journal of Progressive Medical Sciences
Published: 2025-08-31

Abstract

Earth's most common viruses, bacteriophages, infect bacteria and archaea. Protein capsids and sometimes lipid envelopes encase phage genomes, which vary in kind and structure. Most are double-stranded DNA phages, whereas Cystoviridae are RNA. Phages control bacterial populations, transfer horizontal genes, lyse molecules, and alter metabolism in different situations. Based on their structural morphotypes, which are largely determined by tail architecture, phages are classified as Podoviridae (short tails), Siphoviridae (long, flexible tails), and Myoviridae (long, contractile tails). They build genome transport and host recognition virions with portal proteins, tail fibers, and baseplates. DNA is transferred into capsids by ATP-dependent terminases during genome packing.  The lysogenic cycle comprises temperate phages integrating into the host genome as prophages and replicating passively until stimulation activates the lytic phase. Phages with non-lytic chronic infections or carriers exist. Phages limit their host range by recognizing lipopolysaccharides, outer membrane proteins, teichoic acids, and flagella. They can make anti-CRISPR proteins to attack bacteria. Phages indirectly affect human health by influencing microbiota and immune systems. Immunoglobulin-like capsid domains connect them to mucosal surfaces for bacterial clearance and barrier protection. They can also enter tissues and circulation, where they are immunologically tolerated. Phages activate innate and adaptive immunity. Innate sensing and cytokine production are enabled by TLR3, TLR7, and TLR9. However, adaptive immunity produces neutralizing IgM, IgG, and IgA antibodies. Recurrent phage therapy can be reduced by phage-neutralizing antibodies. Phage biology is characterized by the discovery of "huge phages" with genomes that rival small bacterial genomes and encode complex functions like tRNAs, translation factors, CRISPR-Cas systems, and nucleus-like compartments that protect


phage genomes from host defenses. Phage-encoded CRISPR-Cas systems often lack spacer acquisition or interference genes, resulting in host apparatus repurposing or gene transcriptional silence. Targeting competing phages and host regulatory mechanisms is possible.  Phages treat antibiotic-resistant microorganisms. Phage treatment has potential despite bacterial resistance and host immune neutralization. They also carry toxin genes (cholera, diphtheria) through lysogenic conversion, boosting bacterial pathogenicity. Dynamic evolutionary arms races affect microbial ecology through phage-host and phage-phage interactions. Recent metagenomics and meta transcriptomics advances have increased the variety of dsRNA and tailless dsDNA phages. This showed unique viral families and the prevalence of phages in human microbiomes, particularly crAss-like phages in the intestine. The molecular details of phage interactions with eukaryotic cells are still emerging, despite the vast knowledge of bacterial receptors for phage attachment. Mammalian cells can use endocytosis mechanisms to internalize phages for immunological regulation and therapeutic delivery. expanding the taxonomy of dsRNA phages, understanding non-lytic infection mechanisms, characterizing phage-host range and interactions, and using phages for biocontrol in agriculture and medicine. It is required to overcome immune clearance, understand phage immunogenicity, and understand the tri-kingdom interactions between phages, bacteria, and human hosts that maintain microbial and immunological homeostasis to maximize phage therapy. Bacteriophages are complex, diversified, and ecologically important viruses. Bacteria, horizontal gene transfer, immune system contact, and burgeoning biological uses including phage therapy and biotechnology are managed. Phages' complex life cycles, structural biology, and interactions with human and bacterial hosts are being understood beyond their role as bacterial predators. Briefly explain bacteriophages, which infect bacteria and archaea, their diversity, dsDNA and dsRNA phages, structure and replication mechanisms, ecological implications, mammalian immunity, and emerging therapeutic applications, including phage therapy. Phage viruses are assembled by complex structural proteins. Widely studied tailed phages including T7 (Autographviridae/Podoviridae-like), SPP1 (Siphoviridae-like), and T4 (Myoviridae-like) have tail and capsid shapes optimized for genome transport and host recognition Biomolecules such lipopolysaccharides and outer membrane proteins bind to baseplate and tail fibers. Genome packing motor ATPases assist phage DNA enter capsids. T4 phages employ the lytic cycle to rapidly multiply and lyse the host cell, while temperate phages use the lysogenic cycle to passively


integrate their genome into the host chromosome until induction activates lytic replication. Infection-causing pseudolysogenic or persistent phages do not lyse quickly. In bacterial pathogen phage treatment, these life choices affect phage ecology and application.  To identify hosts, phages recognize polysaccharides, proteins, and flagella. Phage host range is limited by specificity. To escape bacterial defenses, phages can encode anti-CRISPR proteins and adapt genomically. Phages transfer toxin genes and other virulence factors to bacteria by lysogenic conversion. Phages influence microbiomes and immunity without infecting humans. Phages can infect tissues and cells via endocytosis, altering immune responses. Phages destroy bacteria to fight antibiotic-resistant illnesses, but immunological responses including neutralizing antibodies can hinder phage treatment. Recent discoveries include "huge phages" with microscopic bacteria genomes. Complex machinery is provided by tRNA, translation factor, and CRISPR-Cas phages. Metagenomic studies have found tailless dsDNA phages from new viral orders and families, enhancing our understanding of phage diversity. CRISPR-mediated phage-host and phage-phage interactions show dynamic evolutionary arms races. Biomedical applications, gene transfer, microbial community dynamics, and bacterial population regulation depend on bacteriophages. Research on their structural biology, trplicative cycles, and host immunological interactions determines their therapeutic and ecological potential. Bacteriophages are everywhere in the biosphere and influence bacterial ecology and evolution. DNA-containing bacteriophages in ecosystems are well-studied, whereas RNA-containing ones are often overlooked.

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