Explore the vast range of titles available.

Bacteriophages, or phages, are viruses of members of domain Bacteria. These viruses play numerous roles in shaping the diversity of microbial communities, with impact differing depending on what infection strategies specific phages employ. From an applied perspective, these especially are communities containing undesired or pathogenic bacteria that can be modified through phage-mediated bacterial biocontrol, that is, through phage therapy. Here we seek to categorize phages in terms of their infection strategies as well as review or suggest more descriptive, accurate or distinguishing terminology. Categories can be differentiated in terms of (1) whether or not virion release occurs (productive infections versus lysogeny, pseudolysogeny and/or the phage carrier state), (2) the means of virion release (lytic versus chronic release) and (3) the degree to which phages are genetically equipped to display lysogenic cycles (temperate versus non-temperate phages). We address in particular the use or overuse of what can be a somewhat equivocal phrase, ‘Lytic or lysogenic’, especially when employed as a means of distinguishing among phages types. We suggest that the implied dichotomy is inconsistent with both modern as well as historical understanding of phage biology. We consider, therefore, less ambiguous terminology for distinguishing between ‘Lytic’ versus ‘Lysogenic’ phage types. The phrase ‘Lytic or lysogenic’ we suggest can be problematic as most phages that display lysogeny also are ‘Lytic’ while bacteria are lysogenic, not phages.

Salmonella Infantis is an emerging pathogen highly associated with antibiotic-resistant issues and has contributed to increasing foodborne illness in recent years. Thus, finding novel antimicrobial agents is urgent for the solution. The objective was to characterize a newly isolated Epseptimavirus phage with antimicrobial activity against multidrug-resistant S. Infantis strains. Salmonella phage vB_(S)alS-SIY1lw (or SIY1lw) is a new member of the phages belonging to the Epseptimavirus genus. SIY1lw contained the receptor binding protein (ORF 23) and tail fiber protein (ORF 43) genes—both associated with bacterial host recognition and binding—similar to that in Salmonella phage OSY-STA (the Epseptimavirus genus) and Escherichia phage DaisyDussoix (the Tequintavirus genus), respectively. For biological traits, SIY1lw has a latent period of 30 min and an estimated burst size of 42 PFU/CFU. The phage was polyvalent against S. enterica (Infantis and Newport) and non-pathogenic E. coli strains. The in vitro antimicrobial activity test showed that the phage with MOI of 1,000 is the most effective in reducing S. Infantis FSIS7823 and FSIS4921 by 1 and 0.8 log, respectively, over the 6-h treatment at 25 °C. These findings indicate that the new Epseptimavirus phage SIY1lw has future potential to develop an antimicrobial alternative to multidrug-resistant S. Infantis strains.

Phage therapy is one of the alternatives to treat infections caused by both antibiotic-sensitive and antibiotic-resistant bacteria, with no or low toxicity to patients. It was started a century ago, although rapidly growing bacterial antimicrobial resistance, resulting in high levels of morbidity, mortality, and financial cost, has initiated the revival of phage therapy. It involves the use of live lytic, bioengineered, phage-encoded biological products, in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body within seven days of clearing an infection. They target specific bacterial strains and cause minimal disruption to the microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying a high phage titer for therapy exposes them and activates the host immune system. To date, no serious side effects have been reported with human phage therapy. In this review, we describe phage-phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, and the therapeutic application of modified phages and phage-encoded products. We also highlight the comparison of antibiotics and lytic phage therapy, the pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling, and current challenges in phage therapy. Keywords: lysogenization, lytic phage, modified phages, resistance to phages, CRISPR, immunity, conquering CRISPR, phage-encoded products

Mobile genetic elements, such as phages and plasmids, are diverse and drive bacterial evolution through horizontal gene transfer. Phage-plasmids, of which many carry antibiotic resistance genes or virulence factors, are both phages and plasmids and have life cycles of temperate phages and plasmids. This makes accurate classification difficult as current computational tools typically classify them as one or the other. We addressed this problem by developing tyPPing, a new and highly precise method, to systematically identify, separate, and catalog phage-plasmids. We demonstrated that tyPPing is highly accurate and broadly compatible. It provides a reliable foundation for all future studies involving phages and plasmids, ranging from agriculture environments to pathogenic strains of clinical settings.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has driven us to explore alternative treatments for the limitation of antimicrobial agents. Lytic phages are considered a promising alternative treatment for CR-hvKP infection. In this study, we reported three novel lytic phages, vB_KpnA_SCNJ1-Z, vB_KpnS_SCNJ1-C, and vB_KpnM_SCNJ1-Y, against a CR-hvKP strain SCNJ1, and they possess genomes of double-stranded DNA with a size of 43,428 bp, 46,039 bp, and 50,360 bp, respectively. Phylogenetic analysis demonstrated that vB_KpnA_SCNJ1-Z belongs to the family Autographiviridae within the class Caudoviricetes , while vB_KpnS_SCNJ1-C and vB_KpnM_SCNJ1-Y are unclassified Caudoviricetes . The phages showed a narrow host range only lysing 1 of 50 tested clinical bacterial strains. The one-step growth curves and stability results showed that the phages displayed relatively short latency periods, with broad pH (pH 3-14) and thermal stabilities (20–60°C). The phages showed significant inhibition of the biofilm formation by SCNJ1 and strong antibacterial activity in vitro . In the mouse model, we demonstrated that administration of a single phage or phage cocktail significantly reduced bacteria loads in the lung, liver, and spleen, and effectively rescued mice from the infection of the SCNJ1 strain, with a survival rate of 70-80%. These findings suggested the three phages have great potential as an alternative therapy with favorable stability and strong antibacterial activity both in vivo and in vitro for the treatment of CR-hvKP infection.

The world is currently facing a global health crisis due to the rapid increase in antimicrobial-resistant bacterial infections. One of the most concerning pathogens is Acinetobacter baumannii, which is listed as a Priority 1 pathogen by the World Health Organization. This Gram-negative bacterium has many intrinsic antibiotic resistance mechanisms and the ability to quickly acquire new resistance determinants from its environment. A limited number of effective antibiotics against this pathogen complicates the treatment of A. baumannii infections. A potential treatment option that is rapidly gaining interest is “phage therapy”, or the clinical application of bacteriophages to selectively kill bacteria. The myoviruses DLP1 and DLP2 (vB_AbaM-DLP_1 and vB_AbaM-DLP_2, respectively) were isolated from sewage samples using a capsule minus variant of A. baumannii strain AB5075. Host range analysis of these phages against 107 A. baumannii strains shows a limited host range, infecting 15 and 21 for phages DLP1 and DLP2, respectively. Phage DLP1 has a large burst size of 239 PFU/cell, a latency period of 20 min, and virulence index of 0.93. In contrast, DLP2 has a smaller burst size of 24 PFU/cell, a latency period of 20 min, and virulence index of 0.86. Both phages show potential for use as therapeutics to combat A. baumannii infections.

Background Carbapenem-resistant Pseudomonas aeruginosa commonly leads to difficult-to-treat infections necessitating new therapeutics. Recently, bacteriophages have gained attention as promising alternatives. This study aimed to isolate, characterize virulent phages from various water sources against clinical carbapenem-resistant P. aeruginosa isolates to formulate a phage cocktail, and evaluate its in vivo efficacy using a mouse burn wound infection model. Results Biological and genomic characterization of isolated phages were determined by host range, temperature and pH stability, transmission electron microscopy analysis, and whole-genome sequencing. Three virulent phages without carrying antibiotic resistance, virulence or lysogeny-related gene included in the study and named as Baskent_P1_112 (Φ1), Baskent_P2_ICU (Φ2) and Baskent_P3_3B (Φ3). Φ1 exhibited podovirus-like morphology, while Φ2 and Φ3 displayed myovirus-like morphology. MOI values were determined as 100, 1, and 10, with corresponding burst sizes of 123, 288 and 115 PFU/CFU, respectively. All three phages were stable at temperatures between 4 and 50 °C; and pH 4–10, Φ1 and Φ3 were completely inactive at pH 2 and 12. Phages with diverse receptor binding site proteins exhibited complementary lytic activity profiles across different and overlapping sets of carbapenem-resistant P. aeruginosa isolates were used for formulation the phage cocktail thereby achieving a broad host range. The therapeutic efficacy of the phage cocktail was compared with antibiotic treatment in 45 Balb/c mice, divided into five groups. Blood and tissue samples were collected for CRP analysis, bacterial load, and histopathological examination. Wound surfaces were measured daily, and survival percentages were recorded. Conclusion Compared to the untreated control group, phage therapy significantly reduced CRP levels and bacterial loads, enhanced wound healing, and improved survival rates without any toxicity. These results demonstrate that the formulated phage cocktail is a promising alternative treatment with a protocol adaptable for on-demand clinical use.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection is one of the global healthcare concerns. Here, we report the phenotypic and genotypic characterization of a novel multi-host Staphylococcus phage RuSa1, isolated from wastewater samples derived from a spotted sambar deer ( Rusa unicolor ) enclosure located at Mangalore, India. Clinical MRSA strains ( n  = 18) susceptible to RuSa1 were genetically and phenotypically diverse as determined by DNA fingerprinting and in vitro culture assays. RuSa1 displayed a latent period and burst size of 10 min and 50 PFU, respectively, and exhibited efficient biofilm removal activities against S. aureus ATCC BAA-44. The phage exhibited moderate UV stability (3 min) and high titre at 4–37 °C and pH 5‒9. RuSa1 possessed a linear double-stranded genomic DNA with a length of 140 kb. The genome contained 30.18% GC composition and shared 82.0‒94.9% sequence similarity with eleven authentic species of Kayvirus recognized by the International Committee on Taxonomy of Viruses based on VIRIDIC analysis. RuSa1 established distinct phyletic lineage in the maximum likelihood phylogenetic analysis of DNA encoding structural proteins and lacked genes that confer lysogeny. Based on the genotypic, phylogenetic and phenotypic data, RuSa1 is proposed to be a lytic phage and a new species of Kayvirus with a potential therapeutic ability against staphylococcal infections.

A novel lytic phage with a broad host range was isolated from pig faeces and the complete genome was subsequently sequenced. The phage was found to lyse Staphylococcus hyicus , S. pseudintermedius , S. schleiferi and S. warneri , generating approximately 27 PFU per infected S. hyicus cell. The phage has an isometric head of 42 ± 2 nm in diameter and a noncontractile tail of 114 ± 9 nm long. The genome is 53,660 bp in size and consists of 79 predicted ORFs and one tRNA Arg gene. The phage has been classified within the Caudoviricetes, specifically the Chaseviridae family. Its broad host range and absence of harmful genes make it suitable for use in phage therapy. In addition, a novel temperate phage was discovered that was spontaneously released from a S. hyicus isolate Pel11 from a pig with exudative epidermitis. This novel temperate phage differs from the known temperate phages in S. hyicus strains NCTC10350, MM2101 or 83/7-1B, representing a novel pathogenicity element in the S. hyicus genome.