Existing studies in bacteriophage biology have largely examined individual components of the phage life cycle alone. These include lysis mechanisms, depolymerases, and developmental pathways. However, successful phage infection depends on the coordinated progression of interconnected events, from developmental commitment to host cell lysis. In this review, we present a systems-level perspective that views the phage lytic cycle as an integrated infection program rather than a collection of independent events. We examine the functional links between environmental sensing, lysis–lysogeny decision-making, population-level communication, host recognition, surface penetration, and terminal lysis, highlighting how each stage influences the next. Understanding these connections is increasingly important for phage engineering and synthetic biology, as a fragmented view can limit the rational design of engineered phages and phage-derived tools. By identifying these molecular nuances that govern productive infection, this review reveals opportunities to develop improved phage-derived enzymes, programmable lysis systems, and next-generation antibacterial therapeutics.
Background: Urinary tract infections (UTIs) are among the most prevalent bacterial infections globally. UTIs are commonly caused by antibiotic-resistant uropathogenic Escherichia coli (UPEC). Phage therapy, using single phage or cocktails, has shown promise as an addition to our options for treating UTIs. Although many phage infecting lab strains of E. coli are known, those are rarely active against UPEC strains. Here, we introduce a newly isolated phage that infects multiple UPEC isolates. Materials and Methods: In this study, Escherichia phage Mizar was isolated from wastewater against the HM03 UPEC clinical isolate. We characterized phage Mizar virion morphology, lysis patterns, adsorption, and infectious cycle parameters via one-step growth assay. Its host range was tested on clinical UPEC isolates and reference strains. The phage Mizar genome was sequenced, annotated, and compared at the nucleotide and protein levels to other Caudoviricetes phages. Results: Mizar is a virulent T4-like myophage that adsorbs to its host HM03 cells within three minutes and completes lysis in 15 min to produce an average of ∼97 phages per cell. Mizar can infect 10 out of the 18 UPEC isolates and reference strains tested. Its double-stranded DNA genome is 170,012 base pairs with a G + C content of 38%. Comparative genomics revealed Mizar classifies within the Straboviridae and is most similar to Escherichia phage ATK47 at the nucleotide level. Conclusions: Phage Mizar effectively infects UPEC classified within both phylogroups A and B, expanding our collection of phages available to investigate for therapeutic use.
Staphylococcus aureus biofilms are a significant cause of persistent and chronic infections, especially on indwelling medical devices. They exhibit mechanisms to resist antibiotics and host immune defenses. The emergence of multidrug-resistant strains like methicillin-resistant S. aureus has intensified the need for alternative therapeutic approaches. Bacteriophage therapy, utilizing viruses that specifically infect and kill bacteria, has regained interest as a potential strategy to combat S. aureus biofilms due to its specificity and ability to disrupt biofilm structure. However, several challenges limit the clinical application of phage therapy against biofilms, including limited penetration of the biofilm matrix, narrow host range, development of phage-resistant bacterial subpopulations, decreased metabolic activity of bacteria within biofilms, and quorum sensing (QS)–mediated defense mechanisms. This review discusses the molecular basis of S. aureus biofilm formation and persistence, summarizes the current advances and limitations of phage therapy targeting biofilms, and explores future perspectives and counterstrategies such as phage engineering, combination therapies, and QS inhibition to enhance therapeutic efficacy. Understanding and overcoming these challenges are critical for advancing phage therapy as a viable treatment option for biofilm-associated S. aureus infections.
Background: Salmonella enterica serovar Typhimurium is a foodborne pathogen, and lytic phages may provide targeted biocontrol. Materials and Methods: S2EK was evaluated for host range, replication, broth growth suppression, stability, and genome characteristics. Results: S2EK lysed its isolation host but did not lyse the 11 heterologous ATCC strains representing 10 bacterial species. The optimal multiplicity of infection was 0.1, the latent period was 30 min, and the mean burst size was 366 plaque-forming units per infected cell. It remained infective at pH 6–8 and 40–70°C. The 42,843-bp genome (49.93% G+C) contained 61 coding sequences and no tRNAs. No integrase or excisionase genes, virulence factors, or antimicrobial-resistance determinants were detected. S2EK was assigned to the subfamily Guernseyvirinae , the genus Jerseyvirus , and the species Jerseyvirus celemicas . Conclusions: S2EK is active against its isolation host. Activity against additional Salmonella strains and efficacy in food matrices require investigation.
Recurrent urinary tract infections (rUTIs)—increasingly due to multidrug-resistant organisms—affect up to half of kidney transplant recipients (KTRs) in the first year and are associated with eGFR decline, rejection, and reduced graft survival. Bacteriophages (phages) offer targeted, microbiome-sparing activity with biofilm penetration and antibiotic synergy that directly address transplant-specific challenges. In this narrative review (search through May 2025), we synthesize evidence spanning clinical reports, mechanistic work, and the emerging regulatory framework. Case series and compassionate-use cohorts show feasibility and safety of personalized phage therapy, with clinical improvement in 77% and microbiological eradication in 61% of difficult infections; randomized data outside transplantation support safety but emphasize the need for pathogen matching. Route selection is pivotal: intravesical delivery achieves high local titers with low systemic immunogenicity for bladder-dominant disease, whereas intravenous phage is suited to bacteremia/upper-tract infection. Regulatory momentum includes the European Pharmacopoeia general chapter 5.31 (2024) and an actively recruiting randomized KTR trial (NCT06409819). To transition from promise to practice, forthcoming trials should preplan phage–antibiotic synergy, integrate immunogenicity monitoring for prolonged IV use, and adopt graft-centric endpoints (UTI-free and antibiotic-free days, eGFR slope, and rejection). Phages represent a rational, repeatable adjunct to protect allograft function amid escalating antimicrobial resistance and deserve rigorous evaluation in KTRs.
