{"doi":"10.1101/2021.08.10.455797","title":"Rapid and strain-specific resistance evolution of\n                  <i>Staphylococcus aureus</i>\n                  against inhibitory molecules secreted by\n                  <i>Pseudomonas aeruginosa</i>","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  <jats:italic>Pseudomonas aeruginosa</jats:italic>\n                  and\n                  <jats:italic>Staphylococcus aureus</jats:italic>\n                  frequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, with\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  usually being the dominant species suppressing\n                  <jats:italic>S. aureus</jats:italic>\n                  through a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, and\n                  <jats:italic>S. aureus</jats:italic>\n                  might be able to evolve resistance against inhibitory molecules deployed by\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  . Here, we used experimental evolution to test this hypothesis by exposing three different\n                  <jats:italic>S. aureus</jats:italic>\n                  strains (Cowan I, 6850, JE2) to the growth-inhibitory supernatant of\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  PAO1 over 30 days. Prior to evolution, we found that\n                  <jats:italic>S. aureus</jats:italic>\n                  strains were inhibited by secreted compounds regulatorily controlled by the PQS quorum-sensing system of\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  . Following evolution,\n                  <jats:italic>S. aureus</jats:italic>\n                  strains were no longer inhibited: we observed that phenotypic adaptations were strain-specific and involved the up-regulation of virulence traits, such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters were the most frequent evolutionary targets. Our work indicates that adaptations of\n                  <jats:italic>S. aureus</jats:italic>\n                  to co-infecting pathogens occurs rapidly and involves both virulence traits and membrane transporters involved in drug resistance. Thus, pathogen evolution could promote species co-existence, complicate treatment options and therefore worsen disease outcome.\n                </jats:p>","journal":null,"year":null,"id":601610,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1542653,"name":"Lukas Schwyter","orcid":null,"position":1,"is_corresponding":false},{"id":3391,"name":"Lucy Poveda","orcid":"0000-0002-5291-5582","position":2,"is_corresponding":false},{"id":484467,"name":"Jonas Grossmann","orcid":"0000-0002-6899-9020","position":3,"is_corresponding":false},{"id":658481,"name":"Rolf Kümmerli","orcid":"0000-0003-4084-6679","position":4,"is_corresponding":false},{"id":1542651,"name":"Selina Niggli","orcid":"0000-0002-1898-4488","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Rapid and strain-specific resistance evolution of\n                  <i>Staphylococcus aureus</i>\n                  against inhibitory molecules secreted by\n                  <i>Pseudomonas aeruginosa</i>","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  <jats:italic>Pseudomonas aeruginosa</jats:italic>\n                  and\n                  <jats:italic>Staphylococcus aureus</jats:italic>\n                  frequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, with\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  usually being the dominant species suppressing\n                  <jats:italic>S. aureus</jats:italic>\n                  through a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, and\n                  <jats:italic>S. aureus</jats:italic>\n                  might be able to evolve resistance against inhibitory molecules deployed by\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  . Here, we used experimental evolution to test this hypothesis by exposing three different\n                  <jats:italic>S. aureus</jats:italic>\n                  strains (Cowan I, 6850, JE2) to the growth-inhibitory supernatant of\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  PAO1 over 30 days. Prior to evolution, we found that\n                  <jats:italic>S. aureus</jats:italic>\n                  strains were inhibited by secreted compounds regulatorily controlled by the PQS quorum-sensing system of\n                  <jats:italic>P. aeruginosa</jats:italic>\n                  . Following evolution,\n                  <jats:italic>S. aureus</jats:italic>\n                  strains were no longer inhibited: we observed that phenotypic adaptations were strain-specific and involved the up-regulation of virulence traits, such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters were the most frequent evolutionary targets. Our work indicates that adaptations of\n                  <jats:italic>S. aureus</jats:italic>\n                  to co-infecting pathogens occurs rapidly and involves both virulence traits and membrane transporters involved in drug resistance. Thus, pathogen evolution could promote species co-existence, complicate treatment options and therefore worsen disease outcome.\n                </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W3191973894","authors":[],"funders":[{"funder_name":"Swiss National Science Foundation","grant_id":"182499","title":"An evolutionary ecology approach to disarm bacterial pathogens, control infections, and understand polymicrobial interactions inside hosts"},{"funder_name":"European Commission","grant_id":"681295","title":"Bacterial cooperation at the individual cell level"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/08/10/2021.08.10.455797.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/08/10/2021.08.10.455797.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2021.08.10.455797","host_type":"publisher"},{"url":"https://doi.org/10.1101/2021.08.10.455797","host_type":"repository"},{"url":"https://doi.org/10.5167/uzh-220108","host_type":""},{"url":"https://europepmc.org/article/PPR/PPR380917","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR380917&type=FILE&fileName=EMS156912-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1128/mbio.03153-22","host_type":""},{"url":"https://dx.doi.org/10.5167/uzh-254035","host_type":""},{"url":"https://dx.doi.org/10.3929/ethz-b-000634322","host_type":""},{"url":"https://dx.doi.org/10.5167/uzh-257053","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/37646506","host_type":""},{"url":"http://dx.doi.org/10.1128/mbio.03153-22","host_type":""},{"url":"https://doaj.org/article/3dae2f80d763441198d8b2227b3339fd","host_type":""},{"url":"https://dx.doi.org/10.1101/2021.08.10.455797","host_type":""},{"url":"https://serval.unil.ch/notice/serval:BIB_45D96DB79476","host_type":""},{"url":"https://serval.unil.ch/resource/serval:BIB_45D96DB79476.P001/REF.pdf","host_type":""},{"url":"http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_45D96DB794767","host_type":""},{"url":"http://hdl.handle.net/20.500.11850/634322","host_type":""},{"url":"https://www.zora.uzh.ch/id/eprint/257053/","host_type":""},{"url":"https://doi.org/10.5167/uzh-257053","host_type":""}],"fields_of_study":["Bacterial biofilms and quorum sensing","Bacterial Genetics and Biotechnology","Biochemical and Structural Characterization","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Pseudomonas aeruginosa","Staphylococcus aureus","Virulence","Microbiology","Biology","Pathogen","Phenotype","Quorum sensing","Strain (injury)","Bacteria","Gene","Genetics","polymicrobial infections","10255 Clinic for Thoracic Surgery","610 Medicine & health","10071 Functional Genomics Center Zurich","competition; microbe-microbe interactions; nosocomial pathogen; pathogen evolution; polymicrobial infections; resistance evolution","resistance evolution","Humans","Pseudomonas Infections","microbe-microbe interactions","610 Medicine &amp; health","microbe-microbe interactions; polymicrobial infections; pathogen evolution; competition; resistance evolution; nosocomial pathogen","2404 Microbiology","10177 Dermatology Clinic","pathogen evolution","Staphylococcal Infections","nosocomial pathogen","QR1-502","Biofilms","2406 Virology","Microbial Interactions","11493 Department of Quantitative Biomedicine","competition","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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