{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:18:58Z","timestamp":1790936338204,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5T32GM008111-35"],"award-info":[{"award-number":["5T32GM008111-35"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CFFROWE21R3"],"award-info":[{"award-number":["CFFROWE21R3"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2025,9,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      is a common upper respiratory tract (URT) pathobiont with high carriage rates in the upper airway disease chronic rhinosinusitis (CRS). CRS is associated with increased prevalence and abundance of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">S. aureus-<\/jats:italic>\n                      secreted toxins are implicated in CRS pathogenesis. Conversely, in CRS disease, the abundance of non-pathogenic commensal species has been observed to decline, leading to microbial dysbiosis that contributes to persistent inflammation. Here, we investigated possible mechanisms\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      could employ to outcompete commensal organisms and contribute to establishing the\n                      <jats:italic toggle=\"yes\">S. aureus-<\/jats:italic>\n                      dominant microbiome found in individuals with CRS. We performed a targeted screen to identify\n                      <jats:italic toggle=\"yes\">S. aureus-<\/jats:italic>\n                      secreted factors that affect the growth and aggregation of a URT commensal bacterium,\n                      <jats:italic toggle=\"yes\">Corynebacterium pseudodiphtheriticum<\/jats:italic>\n                      , which is negatively correlated with\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      in CRS.\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      cell-free conditioned media prevented\n                      <jats:italic toggle=\"yes\">C. pseudodiphtheriticum<\/jats:italic>\n                      aggregation; however, anti-aggregation activity was significantly reduced in\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      mutants lacking a functional accessory gene regulator (agr) quorum-sensing system, phenol-soluble modulin (PSM) transporters, and the PSM toxin \u03b4-toxin. Addition of purified recombinant \u03b4-toxin peptide or a related PSM, PSM\u03b13, inhibited\n                      <jats:italic toggle=\"yes\">C. pseudodiphtheriticum<\/jats:italic>\n                      aggregation and induced dispersal of aggregates. Recombinant \u03b4-toxin also reduced\n                      <jats:italic toggle=\"yes\">C. pseudodiphtheriticum<\/jats:italic>\n                      adherence and aggregation on human nasal epithelial cells. PSMs are known to play a role in biofilm structure and remodeling in staphylococci, and here, we demonstrate that PSMs have activity against other bacteria. These results identify a novel mechanism by which\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      can disrupt the commensal lifestyle of microbes that inhabit the same upper respiratory niche via secreted PSM toxins.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Increased\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        abundance and microbial dysbiosis are associated with the pathogenesis of chronic rhinosinusitis disease. Here, we show that\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        \u03b4-toxin, a secreted phenol-soluble modulin (PSM) toxin, can inhibit the ability of commensal\n                        <jats:italic toggle=\"yes\">Corynebacterium<\/jats:italic>\n                        species to aggregate, adhere to, and grow in association with human nasal epithelial cells. PSMs are known to play a key role in the\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        biofilm life cycle, regulating\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        biofilm structure and detachment; however, a role for these toxins in modifying biofilm and aggregate structures of other bacteria has not been previously demonstrated. These results suggest a potential mechanism for\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        to establish dominance in the upper respiratory tract microbiome in disease through direct antagonism of commensal microbes with PSM toxins.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00183-25","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T13:00:27Z","timestamp":1755176427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["<i>Staphylococcus aureus<\/i>\n                    phenol-soluble modulins have dispersal and anti-aggregation activity towards corynebacteria"],"prefix":"10.1128","volume":"207","author":[{"given":"Joshua T.","family":"Huffines","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy and Critical Care, Department of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-182X","authenticated-orcid":true,"given":"Megan R.","family":"Kiedrowski","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy and Critical Care, Department of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00480-20"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2024.102428"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00187-18"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02664-14"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00129-10"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.11.005"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/0194599810391852"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2016.30.4297"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00218-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/all.14276"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00057"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3228"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2019.12.009"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2017.01.008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22332"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00150"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12040646"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02491-18"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01230"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2019.01.008"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2027"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781683670131.ch41"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00706"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr100370n"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12110678"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.03.045"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/all.13783"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.07.013"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201710-2112OC"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.05.004"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00589-23"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00537-12"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00341-18"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00391.2007"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1097(88)90322-9"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05436-11"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00178"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2004.00401.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.6.907"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3110"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","unstructured":"Wang GZ Warren EA Haas AL Pe\u00f1a AS Kiedrowski MR Lomenick B Chou T-F Bomberger JM Tirrell DA Limoli DH. 2023. Staphylococcal secreted cytotoxins are competition sensing signals for Pseudomonas aeruginosa. bioRxiv. doi:10.1101\/2023.01.29.526047","DOI":"10.1101\/2023.01.29.526047"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01748-23"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01606.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.8717"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/011874-0"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2259"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00445-24"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1177\/1945892418801083"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.104"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25042229"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005341"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.05.003"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00153-21"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00412"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004870"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.8.2430-2438.2004"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115006109"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03157-12"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05490-0"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01851-18"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.221382"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/9781118960608.gbm00026"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188555"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.11.001"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00183-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00183-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:49:53Z","timestamp":1777862993000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jb.00183-25"}},"subtitle":[],"editor":[{"given":"Michael J.","family":"Federle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":64,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,18]]}},"alternative-id":["10.1128\/jb.00183-25"],"URL":"https:\/\/doi.org\/10.1128\/jb.00183-25","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00183-25"}}