Bacteriophages (phages) are viruses that specifically infect bacteria. They are the most abundant biological entities on Earth, with an estimated 10^31 particles. Phages play critical roles in bacterial ecology, evolution, and have applications in medicine and biotechnology.
Phage Structure and Classification
Phages consist of nucleic acid (DNA or RNA, single- or double-stranded) enclosed in a protein capsid, and many have a tail structure for host recognition and genome injection. The most studied group is the Caudovirales (tailed phages), including Myoviridae (long contractile tails, e.g., T4), Siphoviridae (long non-contractile tails, e.g., lambda), and Podoviridae (short tails, e.g., T7). Filamentous phages (Inoviridae, e.g., M13) are long and thin, do not lyse their host, and are extruded from the cell without killing it.
Lytic Cycle
The lytic cycle begins with adsorption, where phage tail fibers or receptor-binding proteins recognize specific bacterial surface structures (LPS, porins, pili, flagella). Genome injection follows as the phage penetrates the cell envelope and injects its nucleic acid into the cytoplasm, with empty capsids remaining attached externally. During replication and assembly, the phage hijacks host machinery for replication, transcription, and translation; structural proteins self-assemble into procapsids, and genomic DNA is packaged by terminase enzymes. Finally, lysis occurs when holins create pores in the inner membrane, allowing endolysins to degrade peptidoglycan, causing osmotic lysis and release of progeny virions (typically 50-200 per cell).
Lysogenic Cycle
Temperate phages (e.g., lambda, P1) can integrate their genome into the bacterial chromosome as a prophage or replicate as a plasmid. The prophage is replicated passively with the host genome, and lysogeny is maintained by repressor proteins (e.g., lambda CI) that block lytic gene expression. Induction occurs when DNA damage (via SOS response) triggers RecA-mediated autocleavage of the repressor, switching to the lytic cycle. Lysogenic conversion occurs when prophages carry genes that alter bacterial phenotype (toxins, virulence factors), such as phage-encoded Shiga toxin in E. coli O157:H7, cholera toxin in Vibrio cholerae, and diphtheria toxin in Corynebacterium diphtheriae.
Phage Therapy
Phage therapy uses lytic phages to treat bacterial infections. Advantages include specificity (does not harm commensal microbiota), self-amplification at infection sites, and activity against multidrug-resistant pathogens. Challenges include narrow host range, bacterial resistance to phages, pharmacokinetics (immune clearance), and regulatory hurdles. Successful applications include treatment of P. aeruginosa infections in cystic fibrosis patients, S. aureus prosthetic joint infections, and personalized phage cocktails for compassionate use.
Biotechnological Applications
Phage display uses filamentous phages (M13) to display foreign peptides fused to coat proteins, enabling antibody library screening and protein evolution. Phage typing uses specific phage panels to identify bacterial strains based on susceptibility patterns, employed in epidemiological surveillance. Diagnostic tools include reporter phages engineered to express luciferase or fluorescent proteins, enabling rapid bacterial detection and identification.
