{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T23:20:36Z","timestamp":1776295236519,"version":"3.50.1"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2026,3,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The latest generation of cystic fibrosis transmembrane conductance regulator-targeted modulator therapy, Elexacaftor\/Tezacaftor\/Ivacaftor (ETI), has significantly improved the clinical outcomes of persons with cystic fibrosis (pwCF) but does not appear to completely eliminate CF respiratory microbial colonization. Here, we analyzed over 4,200 publicly available respiratory microbiomes spanning pre- and post-ETI treatment periods and further stratified by age and type of sample. Our analyses reveal that despite reshaping of community composition by ETI, classical CF pathogens such as\n                      <jats:italic toggle=\"yes\">Pseudomonas<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Staphylococcus<\/jats:italic>\n                      spp. persist in sputum and sinonasal samples, while\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      spp. drastically increase in prevalence and relative abundance post-ETI treatment. Obligate anaerobes such as\n                      <jats:italic toggle=\"yes\">Prevotella<\/jats:italic>\n                      spp.,\n                      <jats:italic toggle=\"yes\">Fusobacterium<\/jats:italic>\n                      spp.,\n                      <jats:italic toggle=\"yes\">Porphyromonas<\/jats:italic>\n                      spp., and\n                      <jats:italic toggle=\"yes\">Veillonella<\/jats:italic>\n                      spp. were readily detected post-ETI. We observed changes in the sputum samples from pwCF post-ETI, with an increase in the relative abundance of\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      spp. and prevalence of\n                      <jats:italic toggle=\"yes\">Prevotella<\/jats:italic>\n                      and a decline in\n                      <jats:italic toggle=\"yes\">Pseudomonas<\/jats:italic>\n                      spp. Analysis of co-occurrence networks revealed mostly positive correlations between the different genera pre- and post-ETI; however, these correlations were reduced in number following ETI treatment, suggesting a disruption of community connectivity. To test one of the hypotheses raised by the computational analyses, we experimentally investigated the relationship between\n                      <jats:italic toggle=\"yes\">Streptococcus sanguinis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Prevotella melaninogenica<\/jats:italic>\n                      in a CF sputum-like medium. Our data suggest that\n                      <jats:italic toggle=\"yes\">S. sanguinis<\/jats:italic>\n                      uses reactive nitrogen species, and likely other factors, to antagonize\n                      <jats:italic toggle=\"yes\">P. melaninogenica<\/jats:italic>\n                      , while\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      protects\n                      <jats:italic toggle=\"yes\">P. melaninogenica<\/jats:italic>\n                      in CF-like culture conditions. Our findings implicate polymicrobial interactions, rather than individual species abundance, in determining microbial persistence and adaptation within the CF airway post-ETI.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The introduction of the latest cystic fibrosis transmembrane conductance regulator (CFTR)-targeted Elexacaftor\/Tezacaftor\/Ivacaftor (ETI) therapy represents a major therapeutic advance for persons with cystic fibrosis (pwCF); however, this therapy does not completely negate respiratory infections and colonization. We leverage large-scale publicly available microbiome data to demonstrate that while ETI therapy alters the respiratory microbial landscape, canonically prevalent and abundant CF pathogens persist in many pwCF and likely maintain ecological relevance through adaptive interactions with other taxa. Our\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        findings also reveal that\n                        <jats:italic toggle=\"yes\">Streptococcus sanguinis<\/jats:italic>\n                        can antagonize\n                        <jats:italic toggle=\"yes\">Prevotella melaninogenica<\/jats:italic>\n                        , and that\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        can provide selective protection to quell this antagonism. These insights highlight the need to consider microbial interactions and community dynamics when evaluating long-term responses to CFTR modulators.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00005-26","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T14:00:55Z","timestamp":1772200855000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>Streptococcus sanguinis<\/i>\n                    antagonizes\n                    <i>Prevotella melaninogenica<\/i>\n                    in the context of the cystic fibrosis respiratory microbiome"],"prefix":"10.1128","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-2948","authenticated-orcid":true,"given":"Bassam","family":"El Hafi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3056-8356","authenticated-orcid":true,"given":"Fabrice","family":"Jean-Pierre","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biologie, Universit\u00e9 de Sherbrooke","place":["Sherbrooke, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6625-6216","authenticated-orcid":true,"given":"Lily","family":"Taub","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0543-402X","authenticated-orcid":true,"given":"Thomas H.","family":"Hampton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-4392","authenticated-orcid":true,"given":"George A.","family":"O'Toole","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"Cystic Fibrosis Foundation. 2024. 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