{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:07:51Z","timestamp":1792804071654,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":163,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP220101526"],"award-info":[{"award-number":["DP220101526"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CSIRO\/UQ Future Science Platform Fellowship"},{"name":"National Health and Medical Research Council Ideas","award":["NHMRC:APP1185399"],"award-info":[{"award-number":["NHMRC:APP1185399"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The development of phage resistance by bacteria is a major barrier that impedes the therapeutic use of phages. Phage training has been proposed as a novel tool that harnesses the evolutionary potential of phages to improve phage infectivity. Both evolutionary and co-evolutionary phage training models have been previously reported to train phages. However, both of these phage training models have been reported able to effectively suppress the emergence of phage-resistant bacteria mutants, thus presenting a contradictory phenomenon. Therefore, in this study, we set out to systematically compare the effectiveness of both evolutionary and co-evolutionary phage training models with regard to phage physiology, infectivity, and genotype. To this end, a natural lytic phage capable of infecting a Klebsiella pneumonia strain was isolated from wastewater and subjected to evolutionary and co-evolutionary phage training for 30\u00a0days. After the phage training, the physiology and genomic characteristics of evolved and co-evolved phages were assessed. Our results demonstrated that both evolved and co-evolved phages exhibit improved bacterial suppression activity and are able to delay the emergence of phage resistance. Furthermore, both phages harbored unique genome mutational changes in different functionally associated phage proteins. Similarly, evolved and co-evolved phage-resistant bacteria mutants that arose post phage infection displayed varying phage resistance sensitivities, which may be correlated to the unique genome mutational change identified in cell membrane structure. In particular, co-evolved phage-resistant bacteria mutants exhibited less phage resistance compared to evolved phage-resistant bacteria mutants. These results highlighted the finding that the co-evolutionary phage training model serves as a better phage training model as it endows phage with improved infectivity, but also selects for phage-resistant bacteria with a lower phage resistance when compared to evolutionary phage training.<\/jats:p>","DOI":"10.1093\/ismeco\/ycae082","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T10:29:49Z","timestamp":1718188189000},"source":"Crossref","is-referenced-by-count":23,"title":["Evolutionary and co-evolutionary phage training approaches enhance bacterial suppression and delay the emergence of phage resistance"],"prefix":"10.1093","volume":"4","author":[{"given":"Lyman","family":"Ngiam","sequence":"first","affiliation":[{"name":"Australian Centre for Water and Environmental Biotechnology, The University of Queensland , 4 Gehrmann Laboratories Building, Research Road, St Lucia, Queensland 4072 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Weynberg","sequence":"additional","affiliation":[{"name":"Australian Centre for Ecogenomics, The University of Queensland , Chemistry Building 68, Cooper Road, St Lucia, Queensland 4072 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Guo","sequence":"additional","affiliation":[{"name":"Australian Centre for Water and Environmental Biotechnology, The University of Queensland , 4 Gehrmann Laboratories Building, Research Road, St Lucia, Queensland 4072 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"2024071014412440800_ref1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3390\/v10070351","article-title":"Resistance development to bacteriophages occurring during bacteriophage therapy","volume":"10","author":"Oechslin","year":"2018","journal-title":"Viruses"},{"key":"2024071014412440800_ref2","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/1574-6976.12072","article-title":"Bacteria\u2013phage coevolution as a driver of ecological and evolutionary processes in microbial communities","volume":"38","author":"Koskella","year":"2014","journal-title":"FEMS Microbiol Rev"},{"key":"2024071014412440800_ref3","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.1073\/pnas.0504062102","article-title":"Coevolutionary arms races between bacteria and bacteriophage","volume":"102","author":"Weitz","year":"2005","journal-title":"Proc Natl Acad Sci"},{"key":"2024071014412440800_ref4","doi-asserted-by":"crossref","first-page":"e2104592118","DOI":"10.1073\/pnas.2104592118","article-title":"Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance","volume":"118","author":"Borin","year":"2021","journal-title":"Proc Natl Acad Sci"},{"key":"2024071014412440800_ref5","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/eva.12085","article-title":"Back to the future: evolving bacteriophages to increase their effectiveness against the pathogen Pseudomonas aeruginosa PAO1","volume":"6","author":"Betts","year":"2013","journal-title":"Evol Appl"},{"key":"2024071014412440800_ref6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3390\/antibiotics8020046","article-title":"Directed evolution of a Mycobacteriophage","volume":"8","author":"Cebri\u00e1","year":"2019","journal-title":"Antibiotics"},{"key":"2024071014412440800_ref7","doi-asserted-by":"crossref","first-page":"11109","DOI":"10.1073\/pnas.1406763111","article-title":"Contrasted coevolutionary dynamics between a bacterial pathogen and its bacteriophages","volume":"111","author":"Betts","year":"2014","journal-title":"Proc Natl Acad Sci"},{"key":"2024071014412440800_ref8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s43705-022-00158-9","article-title":"The presence of plasmids in bacterial hosts alters phage isolation and infectivity","volume":"2","author":"Ngiam","year":"2022","journal-title":"ISME Communications"},{"key":"2024071014412440800_ref9","doi-asserted-by":"crossref","first-page":"5569","DOI":"10.1111\/1462-2920.15714","article-title":"Bacteriophage isolated from non-target bacteria demonstrates broad host range infectivity against multidrug-resistant bacteria","volume":"23","author":"Ngiam","year":"2021","journal-title":"Environ Microbiol"},{"key":"2024071014412440800_ref10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1186\/1471-2164-12-402","article-title":"BLAST ring image generator (BRIG): simple prokaryote genome comparisons","volume":"12","author":"Alikhan","year":"2011","journal-title":"BMC Genomics"},{"key":"2024071014412440800_ref11","volume-title":"Haplotype-Based Variant Detection from Short-Read Sequencing","author":"Garrison","year":"2012"},{"key":"2024071014412440800_ref12","doi-asserted-by":"crossref","DOI":"10.1002\/0471250953.bi1107s32","article-title":"Aligning short sequencing reads with bowtie","volume":"32","author":"Langmead","year":"2010","journal-title":"Curr Protoc Bioinformatics"},{"key":"2024071014412440800_ref13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3390\/ph12010035","article-title":"Phages for phage therapy: isolation, characterization, and host range breadth","volume":"12","author":"Hyman","year":"2019","journal-title":"Pharmaceuticals"},{"key":"2024071014412440800_ref14","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.00066-18","article-title":"Phage therapy in the Postantibiotic era","volume":"32","author":"Gordillo, Altamirano","year":"2019","journal-title":"Clin Microbiol Rev"},{"key":"2024071014412440800_ref15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s43705-023-00299-5","article-title":"Slow growing bacteria survive bacteriophage in isolation","volume":"3","author":"Attrill","year":"2023","journal-title":"ISME Communications"},{"key":"2024071014412440800_ref16","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/j.bpj.2020.09.027","article-title":"On phage adsorption to bacterial chains","volume":"119","author":"Eriksen","year":"2020","journal-title":"Biophys J"},{"key":"2024071014412440800_ref17","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3390\/v4050663","article-title":"Spatial vulnerability: bacterial arrangements, microcolonies, and biofilms as responses to low rather than high phage densities","volume":"4","author":"Abedon","year":"2012","journal-title":"Viruses"},{"key":"2024071014412440800_ref18","doi-asserted-by":"crossref","first-page":"e68562","DOI":"10.1371\/journal.pone.0068562","article-title":"Mapping the tail Fiber as the receptor binding protein responsible for differential host specificity of Pseudomonas aeruginosa bacteriophages PaP1 and JG004","volume":"8","author":"Le","year":"2013","journal-title":"PLoS One"},{"key":"2024071014412440800_ref19","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1038\/s41564-019-0477-7","article-title":"Phage tail fibre assembly proteins employ a modular structure to drive the correct folding of diverse fibres","volume":"4","author":"North","year":"2019","journal-title":"Nat Microbiol"},{"key":"2024071014412440800_ref20","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2020.598305","article-title":"Antibiotic resistance and virulence of Extraintestinal pathogenic Escherichia coli (ExPEC) vary according to molecular types","volume":"11","author":"Duan","year":"2020","journal-title":"Front Microbiol"},{"key":"2024071014412440800_ref21","first-page":"693","article-title":"Bacteriophage: time to Re-evaluate the potential of phage therapy as a promising agent to control multidrug-resistant bacteria","volume":"15","author":"Ghannad","year":"2012","journal-title":"Iran J Basic Med Sci"},{"key":"2024071014412440800_ref22","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1186\/1743-422X-7-358","article-title":"Initiation of bacteriophage T4 DNA replication and replication fork dynamics: a review in the virology journal series on bacteriophage T4 and its relatives","volume":"7","author":"Kreuzer","year":"2010","journal-title":"Virol J"},{"key":"2024071014412440800_ref23","doi-asserted-by":"crossref","first-page":"167799","DOI":"10.1016\/j.jmb.2022.167799","article-title":"Terminase subunits from the pseudomonas-phage E217","volume":"434","author":"Lokareddy","year":"2022","journal-title":"J Mol Biol"},{"key":"2024071014412440800_ref24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.virol.2005.06.039","article-title":"Changes in bacteriophage T7 virion structure at the initiation of infection","volume":"340","author":"Kemp","year":"2005","journal-title":"Virology"},{"key":"2024071014412440800_ref25","doi-asserted-by":"crossref","first-page":"6768","DOI":"10.1128\/JVI.00412-12","article-title":"Capsid structure and its stability at the late stages of bacteriophage SPP1 assembly","volume":"86","author":"White","year":"2012","journal-title":"J Virol"},{"key":"2024071014412440800_ref26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s10295-005-0064-1","article-title":"Colanic acid is an exopolysaccharide common to many enterobacteria isolated from paper-machine slimes","volume":"33","author":"R\u00e4tt\u00f6","year":"2006","journal-title":"J Ind Microbiol Biotechnol"},{"key":"2024071014412440800_ref27","doi-asserted-by":"crossref","DOI":"10.1128\/ecosalplus.esp-0001-2018","article-title":"Function and biogenesis of lipopolysaccharides","volume":"8","author":"Bertani","year":"2018","journal-title":"EcoSal Plus"},{"key":"2024071014412440800_ref28","doi-asserted-by":"crossref","first-page":"e1007749","DOI":"10.1371\/journal.pgen.1007749","article-title":"Genome-wide CRISPR-dCas9 screens in E. Coli identify essential genes and phage host factors","volume":"14","author":"Rousset","year":"2018","journal-title":"PLoS Genet"},{"key":"2024071014412440800_ref29","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1128\/AEM.02606-14","article-title":"Phage-encoded Colanic acid-degrading enzyme permits lytic phage infection of a capsule-forming resistant mutant Escherichia coli strain","volume":"81","author":"Kim","year":"2015","journal-title":"Appl Environ Microbiol"},{"key":"2024071014412440800_ref30","doi-asserted-by":"crossref","first-page":"fnw002","DOI":"10.1093\/femsle\/fnw002","article-title":"Host receptors for bacteriophage adsorption","volume":"363","author":"Bertozzi Silva","year":"2016","journal-title":"FEMS Microbiol Lett"},{"key":"2024071014412440800_ref31","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1111\/jeb.14095","article-title":"Arms race and fluctuating selection dynamics in Pseudomonas aeruginosa bacteria coevolving with phage OMKO1","volume":"35","author":"Kortright","year":"2022","journal-title":"J Evol Biol"},{"key":"2024071014412440800_ref32","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1098\/rspb.2001.1945","article-title":"Antagonistic coevolution between a bacterium and a bacteriophage","volume":"269","author":"Buckling","year":"2002","journal-title":"Proc R Soc Lond Ser B Biol Sci"},{"key":"2024071014412440800_ref33","doi-asserted-by":"crossref","first-page":"17112","DOI":"10.1038\/nmicrobiol.2017.112","article-title":"Bacteriophage evolution differs by host, lifestyle and genome","volume":"2","author":"Mavrich","year":"2017","journal-title":"Nat Microbiol"},{"key":"2024071014412440800_ref34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/bies.201000071","article-title":"The phage-host arms race: shaping the evolution of microbes","volume":"33","author":"Stern","year":"2011","journal-title":"BioEssays"},{"key":"2024071014412440800_ref35","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.coviro.2013.07.001","article-title":"Viral host-adaptation: insights from evolution experiments with phages","volume":"3","author":"Hall","year":"2013","journal-title":"Current Opinion in Virology"}],"container-title":["ISME Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ismecommun\/advance-article-pdf\/doi\/10.1093\/ismeco\/ycae082\/58208335\/ycae082.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ismecommun\/article-pdf\/4\/1\/ycae082\/58495642\/ycae082.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ismecommun\/article-pdf\/4\/1\/ycae082\/58495642\/ycae082.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T11:33:12Z","timestamp":1720611192000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ismecommun\/article\/doi\/10.1093\/ismeco\/ycae082\/7691755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,8]]}},"URL":"https:\/\/doi.org\/10.1093\/ismeco\/ycae082","relation":{},"ISSN":["2730-6151"],"issn-type":[{"value":"2730-6151","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2024,1]]},"article-number":"ycae082"}}