PHAGE (New Rochelle, N.Y.)最新文献

{"title":"\"Two Is Better Than One\": The Multifactorial Nature of Phage-Antibiotic Combinatorial Treatments Against ESKAPE-Induced Infections.","authors":"Gale Bernice N Fungo, John Christian W Uy, Kristiana Louise J Porciuncula, Chiarah Mae A Candelario, Deneb Philip S Chua, Tracey Antaeus D Gutierrez, Martha Rebecca Jane Clokie, Donna May D Papa","doi":"10.1089/phage.2023.0007","DOIUrl":"10.1089/phage.2023.0007","url":null,"abstract":"<p><p>Phage-antibiotic synergy (PAS) has been extensively explored over the past decade, with the aim of developing more effective treatments against multidrug-resistant organisms. However, it remains unclear how to effectively combine these two approaches. To address this uncertainty, we assessed four main aspects of PAS interactions in this review, seeking to identify commonalities of combining treatments within and between bacterial species. We examined all literature on PAS efficacy toward ESKAPE pathogens and present an analysis of the data in papers focusing on: (1) order of treatment, (2) dose of both phage and antibiotics, (3) mechanism of action, and (4) viability of transfer from <i>in vivo</i> or animal model trials to clinical applications. Our analysis indicates that there is little consistency within phage-antibiotic therapy regimens, suggesting that highly individualized treatment regimens should be used. We propose a set of experimental studies to address these research gaps. We end our review with suggestions on how to improve studies on phage-antibiotic combination therapy to advance this field.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 2","pages":"55-67"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9715644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and Characterization of Phages That Bypass the Requirement for RNA-Mediated Antitermination.","authors":"Rodney A King, Millicent Babbs, Kimberly Baugh, Courtney Hamilton","doi":"10.1089/phage.2023.0008","DOIUrl":"10.1089/phage.2023.0008","url":null,"abstract":"<p><strong>Introduction: </strong>The <i>rpoC</i>Y75N mutation in the zinc-binding domain of the β' subunit of <i>Escherichia coli</i> RNA polymerase blocks the RNA-based mechanism of transcription antitermination utilized by bacteriophage HK022.</p><p><strong>Materials and methods: </strong>Mutant phages that overcome the block imposed by the <i>rpoC</i>Y75N mutation are described. These phages, designated \"<i>orc</i>\" (overcomes <i>rpoC</i>), carry mutations that create new promoters. Promoter activity was assessed by cloning the respective regions from the wild-type and <i>orc</i> phages into a promoterless <i>lacZ</i> reporter vector.</p><p><strong>Results: </strong>Reporter assays showed that the sequence originating from <i>orc</i> phages had significant promoter activity when compared with the equivalent sequence cloned from the parental phage.</p><p><strong>Conclusions: </strong>The newly created promoters facilitate the expression of phage genes that are essential for growth on the <i>rpoC</i>Y75N strain by bypassing transcription terminators. The small plaque phenotype of <i>orc</i> phages, when grown on the mutant host, suggests that suppression of the <i>rpoC</i>Y75N mutation is incomplete.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 2","pages":"82-89"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Bacteriophages Members of the <i>Ackermannviridae</i> Family Specific for <i>Klebsiella pneumoniae</i> ST258.","authors":"Estefanía Tisalema-Guanopatín, Fausto Cabezas-Mera, Karla Nolivos-Rodríguez, Isabel Fierro, Lourdes Pazmiño, Daniel Garzon-Chavez, Alexis Debut, Karla Vizuete, Jorge Aníbal Reyes","doi":"10.1089/phage.2022.0039","DOIUrl":"10.1089/phage.2022.0039","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant <i>Klebsiella pneumoniae</i>, particularly isolates classified as sequence-type 258 (ST258), are multidrug-resistant strains that are strongly associated with poor-prognosis nosocomial infections, as current therapeutic options are limited and ineffective. In recent years, phage therapy has emerged as a promising treatment option for these scenarios.</p><p><strong>Methodology and results: </strong>We report the isolation and characterization of three new phages against <i>Klebsiella pneumoniae</i> ST258 strains recovered from Machángara river wastewater. These new members of the <i>Ackermannviridae</i> family showed stability over a wide temperature and pH range and burst sizes ranging from 6 to 44 plaque-forming units per bacteria. Their genomes were about 157 kilobases, with an average guanine-cytosine content of 46.4% and showed presence of several transfer RNAs, which also allowed us to predict <i>in silico</i> a lytic replicative cycle due to the presence of endolysins and lysozymes.</p><p><strong>Conclusion: </strong>Three lytic phages of <i>Ackermannviridae</i> family were recovered against <i>Klebsiella pneumoniae</i> ST258 strains from sewage; however, further characterization is needed for future consideration as therapeutic alternatives.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 2","pages":"99-107"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9715638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phage Therapy Administration Route, Regimen, and Need for Supplementary Antibiotics in Patients with Chronic Suppurative Lung Disease.","authors":"Jessica Williams, James Severin, Ben Temperton, Philip J Mitchelmore","doi":"10.1089/phage.2022.0036","DOIUrl":"10.1089/phage.2022.0036","url":null,"abstract":"<p><p>Antimicrobial resistance is leading to increased mortality, posing risk to those with chronic suppurative lung disease (CSLD). One therapeutic option may be to target treatment-resistant bacteria using viruses (bacteriophages [phages]). Currently, patients receiving phage therapy on compassionate grounds may not be receiving optimal treatment as there is no defined approach for phage use. This review aims to explore administration route, regimen, and need for supplementary antibiotics in phage therapy to treat bacterial infection in CSLD. Twelve articles totaling 18 participants included details of numerous phage administration routes with varying regimens. All articles reported an initial reduction of bacterial load or an improvement in patient symptoms, highlighting the potential of phage therapy in CSLD. Fifteen out of 18 used supplementary antibiotics. Standardized protocols informed by high-quality research are necessary to ensure safe and effective phage therapy. In the interim, systematic recording of information within case reports may be useful.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"4-10"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9556963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of a Bacteriophage Cocktail to Control <i>Salmonella</i> Growth <i>Ex Vivo</i> in Avian, Porcine, and Human Epithelial Cell Cultures.","authors":"Janet Y Nale, Buthainah Ahmed, Richard Haigh, Jinyu Shan, Preeda Phothaworn, Parameth Thiennimitr, Angela Garcia, Manal AbuOun, Muna F Anjum, Sunee Korbsrisate, Edouard E Galyov, Danish J Malik, Martha R J Clokie","doi":"10.1089/phage.2023.0001","DOIUrl":"10.1089/phage.2023.0001","url":null,"abstract":"<p><p>We examined the activity of phages to control the growth of chicken and swine <i>Salmonella</i> strains in avian (CHIC-8E11), porcine (IPEC-1), and human (HT-29) cell cultures. We optimized a six-phage cocktail by selecting the five most effective myoviruses and a siphovirus that have optimal lysis on prevalent serovars. We observed ∼20% of 7 log₁₀ PFU/well phage and 3-6 log₁₀ CFU bacterial adhesions, and 3-5 log₁₀ CFU bacterial invasion per 2 cm² of the cultured cells at 2 h post-treatment. The invasive bacteria when plated had a variable reduced susceptibility to the phages. After phage application at an MOI of 10, the prophylaxis regimen had better efficacy at controlling bacterial growth with an up to 6 log₁₀ CFU/well reduction as compared with the 1-2 log₁₀ CFU/well bacterial reduction observed in the remedial and coinfection regimens. Our data support the development of these phages to control salmonellosis in chickens, pigs, and humans.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"11-25"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9556964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Representative Collection of Commensal Extended-Spectrum- and AmpC-β-Lactamase-Producing <i>Escherichia coli</i> of Animal Origin for Phage Sensitivity Studies.","authors":"Amira R Vitt, Martine C Holst Sørensen, Valeria Bortolaia, Lone Brøndsted","doi":"10.1089/phage.2023.0002","DOIUrl":"10.1089/phage.2023.0002","url":null,"abstract":"<p><strong>Introduction: </strong>Extended-spectrum β-lactamase (ESBL)- and AmpC β-lactamase (AmpC)-producing <i>Escherichia coli</i> from livestock and meat represent a zoonotic risk and biocontrol solutions are needed to prevent transmission to humans.</p><p><strong>Methods: </strong>In this study, we established a representative collection of animal-origin ESBL/AmpC <i>E. coli</i> as target to test the antimicrobial potential of bacteriophages.</p><p><strong>Results: </strong>Bioinformatic analysis of whole-genome sequence data of 198 ESBL/AmpC <i>E. coli</i> from pigs, broilers, and broiler meat identified strains belonging to all known <i>E. coli</i> phylogroups and 65 multilocus sequence types. Various ESBL/AmpC genes and plasmid types were detected with expected source-specific patterns. Plaque assay using 15 phages previously isolated using the <i>E. coli</i> reference collection demonstrated that <i>Warwickvirus</i> phages showed the broadest host range, killing up to 26 strains.</p><p><strong>Conclusions: </strong>154/198 strains were resistant to infection by all phages tested, suggesting a need for isolating phages specific for ESBL/AmpC <i>E. coli</i>. The strain collection described in this study is a useful resource fulfilling such need.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"35-45"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lungs, Liposomes, Libraries, and Likely Interactions Between Phages and Eukaryotic Cells.","authors":"Martha Clokie, Thomas Sicheritz-Pontén","doi":"10.1089/phage.2023.29041.editorial","DOIUrl":"10.1089/phage.2023.29041.editorial","url":null,"abstract":"","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cartoon.","authors":"","doi":"10.1089/phage.2023.29040.car","DOIUrl":"10.1089/phage.2023.29040.car","url":null,"abstract":"","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole Genome Sequence of a Novel Bacteriophage APT65 Infecting <i>Aeromonas hydrophila</i>.","authors":"Ayşe Cebeci, Mustafa Türe, Melike Alemdağ, Ilhan Altinok","doi":"10.1089/phage.2022.0037","DOIUrl":"10.1089/phage.2022.0037","url":null,"abstract":"<p><strong>Background: </strong><i>Aeromonas hydrophila</i> is a prevalent pathogenic bacterium in aquaculture that causes economic loss around the world. Antimicrobials are used to control and prevent the incidence of bacterial pathogens in aquaculture. However, they lead to the emergence of antimicrobial resistance strains and the accumulation of antibiotic residues in fish tissue. To address these issues, bacteriophages may be promising alternatives to many antibiotics in combating bacterial infections in aquaculture.</p><p><strong>Materials and methods: </strong>The phage specific to <i>A. hydrophila</i> was isolated from domestic wastewater. The morphology of phages was analyzed using transmission electron microscopy. The genomic DNA of the Aeromonas phage T65 strain (APT65) phage was sequenced with a paired-end read length of 2 × 150 bp. The genome sequence was assembled and annotated. The tRNAs were predicted, and antimicrobial resistance and virulence genes were screened. A representation of the APT65 genome was constructed.</p><p><strong>Results: </strong>The genome of APT65 is linear double-stranded DNA with 85188 base pairs having 116 open reading frames (ORFs) and a G + C content of 39.41%. The 32 ORFs were predicted to encode proteins with known phage functions. No virulence factors, antibiotic resistance genes, or temperate lifestyle genes were found. The phage is icosahedral and measures 60 nm in diameter. Based on the whole genome sequence, APT65 belongs to <i>Lahexavirus</i>.</p><p><strong>Conclusions: </strong>The taxonomic analysis of the phage with a genome length of 85,188 bp revealed that it is a new species of the genus <i>Lahexavirus</i>. We announce the whole genome sequence of APT65, which should be named <i>Lahexavirus</i> APT65, as well as the absence of antimicrobial resistance and virulence factors from its genome. Based on our results, the <i>Lahexavirus</i> APT65 phage may have potential as a therapeutic agent to tackle antimicrobial resistance in aquaculture.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"46-50"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic Evaluation in HaCaT Cells of the Pa.7 Bacteriophage from <i>Cutibacterium</i> (<i>Propionibacterium</i>) <i>acnes</i>, Free and Encapsulated Within Liposomes.","authors":"Daniela Torres Di Bello, Diana M Narváez, Helena Groot de Restrepo, Martha J Vives","doi":"10.1089/phage.2022.0038","DOIUrl":"10.1089/phage.2022.0038","url":null,"abstract":"<p><strong>Introduction: </strong>Acne is a multifactorial disease involving the colonization of skin follicles by <i>Cutibacterium</i> (formerly <i>Propionibacterium</i>) <i>acnes</i>. A combination of different retinoid-derived products, antibiotics, and hormonal antiandrogens are used to treat the disease, but these treatments require extended periods, may have secondary effects, are expensive, and not always effective. Owing to antibiotic resistance, the use of bacteriophages has been proposed as an alternative treatment. However, if they are intended for a cosmetic or pharmaceutical use, it is necessary to evaluate the safety of the phages and the preparations containing them.</p><p><strong>Materials and methods: </strong>In this study, the cytotoxicity of Pa.7 bacteriophage was evaluated in HaCaT cells, along with a liposome suitable for their encapsulation, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays.</p><p><strong>Results: </strong>We found that Pa.7 was not cytotoxic for HaCaT cells. Also, 30 mM of liposomes, or below are considered noncytotoxic concentrations.</p><p><strong>Conclusion: </strong>Phages encapsulated in the liposomes presented in this study can be used safely for skin treatments.</p>","PeriodicalId":74428,"journal":{"name":"PHAGE (New Rochelle, N.Y.)","volume":"4 1","pages":"26-34"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9556965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}