Journal of Cystic Fibrosis最新文献

{"title":"Poster: 58Evaluating CFTR G551D transgenic ferrets as an animal model for Mycobacteroides abscessus lung infection in CF","authors":"N. Gokanapudi, T. Gupta, K. Sakamoto, B. Ross, A. Stecenko, J. Engelhardt, F. Quinn, B. Rada","doi":"10.1016/j.jcf.2026.07.090","DOIUrl":"10.1016/j.jcf.2026.07.090","url":null,"abstract":"<div><h3>Background</h3><div><em>Mycobacteroides abscessus</em> has emerged as a multidrug resistant pathogen within the cystic fibrosis (CF) population. This bacterium exhibits morphological dimorphism: smooth (S) or rough (R) colony variants. Despite its clinical urgency, the study of <em>M. abscessus</em> pathogenesis and the development of novel therapeutics have been hindered by the lack of relevant animal models. Conventional murine models fail to achieve sustained bacterial colonization. To address this gap, we utilized the transgenic CFTR-G551D ferret model to establish chronic <em>M. abscessus</em> pulmonary infection. Ferrets are uniquely suited for CF research due to their anatomical and physiological similarities to human lungs.</div></div><div><em>Mycobacteroides abscessus</em> has emerged as a multidrug resistant pathogen within the cystic fibrosis (CF) population. This bacterium exhibits morphological dimorphism: smooth (S) or rough (R) colony variants. Despite its clinical urgency, the study of <em>M. abscessus</em> pathogenesis and the development of novel therapeutics have been hindered by the lack of relevant animal models. Conventional murine models fail to achieve sustained bacterial colonization. To address this gap, we utilized the transgenic CFTR-G551D ferret model to establish chronic <em>M. abscessus</em> pulmonary infection. Ferrets are uniquely suited for CF research due to their anatomical and physiological similarities to human lungs.</div><div><h3>Methods</h3><div>To evaluate the longitudinal dynamics of infection, CFTR G551D ferrets (N=11) were infected intratracheally with either smooth or rough morphotype of <em>M. abscessus</em> isolated from the same CF patient (Emory IRB#00042577). Baseline physiological parameters were established via the collection of pre-infection sera and nasal lavage fluid. Following a 4-week stabilization period, serial nasal wash and blood samples were collected bi-weekly to perform ELISA for the quantification of the humoral immune response (anti-<em>M. abscessus</em> antibodies) against heat-killed, gamma-irradiated, and whole-cell lysates of each bacterial morphotype. At the 12-week study endpoint, a comprehensive necropsy was performed to harvest nasal wash, blood, bronchoalveolar lavage, spleen, lungs, and liver. To assess systemic dissemination, tissue samples were homogenized and quantitatively cultured on selective media. To distinguish <em>M. abscessus</em> from microflora endemic to the G551D ferrets, recovered colonies were validated via PCR using species-specific primers.</div></div><div>To evaluate the longitudinal dynamics of infection, CFTR G551D ferrets (N=11) were infected intratracheally with either smooth or rough morphotype of <em>M. abscessus</em> isolated from the same CF patient (Emory IRB#00042577). Baseline physiological parameters were established via the collection of pre-infection sera and nasal lavage fluid. Following a 4-week stabilization period, serial na","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 28-29"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 7Pseudomonas aeruginosa virulence factors pyocyanin and 1-hydroxyphenazine show strong synergism and iron-dependent toxicity in reporter airway cells","authors":"V. Mossine, D. Chance, J. Waters, T. Mawhinney","doi":"10.1016/j.jcf.2026.07.039","DOIUrl":"10.1016/j.jcf.2026.07.039","url":null,"abstract":"<div><h3>Background</h3><div>Historically, cystic fibrosis (CF) pathology included a vicious cycle of chronic respiratory infection, inflammation and obstruction leading to lung damage. Advanced therapeutics are improving exocrine systems functions and quality of life, yet chronic infection and inflammation remain major CF health challenges. <em>Pseudomonas aeruginosa</em> (PA) is a key player in CF infections. PA virulence factors, including pyocyanin (PYO) and related 1-hydroxyphenazine (1HP), phenazine-1-carboxylic acid, and phenazine-1-carboxamide, are seen as potential inducers of chronic inflammation, but mechanisms of their concomitant detrimental effects are not well understood. Here we present novel evidence from laboratory reporter cells of how specific PA phenazines and their combinations may contribute to CF airway pathology.</div></div><div>Historically, cystic fibrosis (CF) pathology included a vicious cycle of chronic respiratory infection, inflammation and obstruction leading to lung damage. Advanced therapeutics are improving exocrine systems functions and quality of life, yet chronic infection and inflammation remain major CF health challenges. <em>Pseudomonas aeruginosa</em> (PA) is a key player in CF infections. PA virulence factors, including pyocyanin (PYO) and related 1-hydroxyphenazine (1HP), phenazine-1-carboxylic acid, and phenazine-1-carboxamide, are seen as potential inducers of chronic inflammation, but mechanisms of their concomitant detrimental effects are not well understood. Here we present novel evidence from laboratory reporter cells of how specific PA phenazines and their combinations may contribute to CF airway pathology.</div><div><h3>Methods</h3><div>Into genomic DNA of human monocyte/macrophage, bronchial epithelial, and alveolar cell lines were introduced a set of PiggyBac transposons containing insulated constructs of transcriptional response elements concatenated with firefly luciferase and green fluorescent protein. Resulting reporter cell lines were challenged with PA phenazines and assessed for viability and activation of transcription factors (TFs) downstream of pro-inflammatory and cellular stress signaling pathways, including NF-κB, Nrf2, STAT1, AP-1, ATF6, etc. Inhibitors tested for modes of death and antioxidants addressed cytotoxicities.</div></div><div>Into genomic DNA of human monocyte/macrophage, bronchial epithelial, and alveolar cell lines were introduced a set of PiggyBac transposons containing insulated constructs of transcriptional response elements concatenated with firefly luciferase and green fluorescent protein. Resulting reporter cell lines were challenged with PA phenazines and assessed for viability and activation of transcription factors (TFs) downstream of pro-inflammatory and cellular stress signaling pathways, including NF-κB, Nrf2, STAT1, AP-1, ATF6, etc. Inhibitors tested for modes of death and antioxidants addressed cytotoxicities.</div><div><h3>Results</h3><div>THP-1, BEAS","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 3-4"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 94Development of bacteriophage resistance by Pseudomonas aeruginosa in a model for phage therapy","authors":"R. Martin, P. Zamora, S. Katzenell, J. Bomberger","doi":"10.1016/j.jcf.2026.07.126","DOIUrl":"10.1016/j.jcf.2026.07.126","url":null,"abstract":"<div><h3>Background</h3><div>With the rise of antibiotic resistance, there is a growing need to develop alternative approaches to treating bacterial infections. This issue is especially salient for people with cystic fibrosis (CF), whose lungs are often subject to chronic colonization by bacterial pathogens. The use of lytic bacteriophages (phages)- viruses that selectively infect and kill their bacterial hosts- is a promising area of research. Their specificity is a strength over traditional antibiotic therapy, allowing phage therapy to target specific bacterial species. This reduces the relative impact on the broader bacterial community; on the other hand, the influence of the bacterial community on phage therapy’s efficacy is not well understood.</div></div><div>With the rise of antibiotic resistance, there is a growing need to develop alternative approaches to treating bacterial infections. This issue is especially salient for people with cystic fibrosis (CF), whose lungs are often subject to chronic colonization by bacterial pathogens. The use of lytic bacteriophages (phages)- viruses that selectively infect and kill their bacterial hosts- is a promising area of research. Their specificity is a strength over traditional antibiotic therapy, allowing phage therapy to target specific bacterial species. This reduces the relative impact on the broader bacterial community; on the other hand, the influence of the bacterial community on phage therapy’s efficacy is not well understood.</div><div><h3>Methods</h3><div>We measured the effects of treatment with a clinically relevant phage, LPS-5, on <em>Pseudomonas aeruginosa</em> (Pa) in single-species Pa biofilms and in a model CF respiratory microbiome (MCFRM) consisting of Pa, <em>Staphylococcus aureus, Streptococcus sanguinis</em>, and <em>Prevotella melaninogenica</em> [1]. Experiments were conducted in synthetic CF sputum media (SCFM5). Bacteria and phage populations were measured by colony and plaque counts, respectively.</div></div><div>We measured the effects of treatment with a clinically relevant phage, LPS-5, on <em>Pseudomonas aeruginosa</em> (Pa) in single-species Pa biofilms and in a model CF respiratory microbiome (MCFRM) consisting of Pa, <em>Staphylococcus aureus, Streptococcus sanguinis</em>, and <em>Prevotella melaninogenica</em> [1]. Experiments were conducted in synthetic CF sputum media (SCFM5). Bacteria and phage populations were measured by colony and plaque counts, respectively.</div><div><h3>Results</h3><div>Our data showed that phage therapy significantly reduced bacterial growth in the first 24 hours (p = < 0.0001 in monoculture Pa and MCFRM conditions). However, at 72 hours, the Pa population began to recover, reducing the difference between untreated and phage-treated populations for both monoculture Pa and the MCFRM (p > 0.05). There were no significant differences between Pa survival in the monoculture and MCFRM conditions. In the MCFRM, there were no significant c","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 47"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 28Antibiotic-driven resistance in Pseudomonas aeruginosa follows nonlinear, state-dependent dynamics in people with cystic fibrosis","authors":"C. Karakoç, S. Brown","doi":"10.1016/j.jcf.2026.07.060","DOIUrl":"10.1016/j.jcf.2026.07.060","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic resistance in <em>Pseudomonas aeruginosa</em> (PA) is a major driver of clinical decline in people with cystic fibrosis (pwCF), yet the eco-evolutionary dynamics linking antibiotic exposures to resistance outcomes remain poorly understood. Standard regression approaches may miss the nonlinear, state-dependent processes that characterize resistance evolution in chronic polymicrobial infections. We developed a multi-method analytical framework integrating Bayesian generalized linear mixed models (GLMMs), Markov chain transition analysis, and empirical dynamic modeling (EDM) to quantify these dynamics using longitudinal clinical data.</div></div><div>Antibiotic resistance in <em>Pseudomonas aeruginosa</em> (PA) is a major driver of clinical decline in people with cystic fibrosis (pwCF), yet the eco-evolutionary dynamics linking antibiotic exposures to resistance outcomes remain poorly understood. Standard regression approaches may miss the nonlinear, state-dependent processes that characterize resistance evolution in chronic polymicrobial infections. We developed a multi-method analytical framework integrating Bayesian generalized linear mixed models (GLMMs), Markov chain transition analysis, and empirical dynamic modeling (EDM) to quantify these dynamics using longitudinal clinical data.</div><div><h3>Methods</h3><div>We analyzed longitudinal data from 114 pwCF across 983 visits at the Emory CF Center, comprising ∼3,300 culture reports with susceptibility profiles across four drug classes (carbapenems, aminoglycosides, fluoroquinolones, cephalosporins) and prescription records for five antibiotic classes. Temporally lagged Bayesian GLMMs predicted resistance at visit <em>t</em>+1 from prescriptions and ecological covariates at visit <em>t</em>. Markov chain models estimated resistance state transitions and steady-state equilibria. EDM with convergent cross-mapping (CCM) tested causal relationships, and S-map analysis characterized nonlinear, state-dependent treatment effects.</div></div><div>We analyzed longitudinal data from 114 pwCF across 983 visits at the Emory CF Center, comprising ∼3,300 culture reports with susceptibility profiles across four drug classes (carbapenems, aminoglycosides, fluoroquinolones, cephalosporins) and prescription records for five antibiotic classes. Temporally lagged Bayesian GLMMs predicted resistance at visit <em>t</em>+1 from prescriptions and ecological covariates at visit <em>t</em>. Markov chain models estimated resistance state transitions and steady-state equilibria. EDM with convergent cross-mapping (CCM) tested causal relationships, and S-map analysis characterized nonlinear, state-dependent treatment effects.</div><div><h3>Results</h3><div>Bayesian GLMMs identified prior resistance, pulmonary exacerbation, colistin prescription, and mucoid phenotype as significant predictors of PA resistance, while cephalosporin exposure was protective. Colistin use promoted cross-resi","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 14"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 89The role of macrophage Piezo1 on bacterial clearance in cystic fibrosis","authors":"E. Orsini, S. Abraham, A. Boulton, H. Ricci, D. Culver, M. Olman, T. Bonfield, T. Kelley, M. Drumm, R. Scheraga","doi":"10.1016/j.jcf.2026.07.121","DOIUrl":"10.1016/j.jcf.2026.07.121","url":null,"abstract":"<div><h3>Background</h3><div>Cystic Fibrosis (CF) macrophage dysfunction is an important driver of CF chronic lung infection and infection-induced lung stiffness. In CF, macrophages fail to clear pathogens, such as <em>Pseudomonas aeruginosa</em>, due to failure of phagolysosome acidification and fusion, known as phagolysosome maturation. Our lab has shown that the macrophage mechanosensitive ion channel, Piezo1, augments phagolysosome maturation on infected lung matrix stiffness (25 kPa) to increase bacterial clearance of CF pathogen, <em>P. aeruginosa</em>. Although the lung matrix stiffness is significantly altered in CF, the role of Piezo1 on macrophage function remains poorly understood. Therefore, we seek to determine if changes to Piezo1 expression or Ca<sup>2+</sup> channel activity drive impaired phagolysosome maturation in CF.</div></div><div>Cystic Fibrosis (CF) macrophage dysfunction is an important driver of CF chronic lung infection and infection-induced lung stiffness. In CF, macrophages fail to clear pathogens, such as <em>Pseudomonas aeruginosa</em>, due to failure of phagolysosome acidification and fusion, known as phagolysosome maturation. Our lab has shown that the macrophage mechanosensitive ion channel, Piezo1, augments phagolysosome maturation on infected lung matrix stiffness (25 kPa) to increase bacterial clearance of CF pathogen, <em>P. aeruginosa</em>. Although the lung matrix stiffness is significantly altered in CF, the role of Piezo1 on macrophage function remains poorly understood. Therefore, we seek to determine if changes to Piezo1 expression or Ca<sup>2+</sup> channel activity drive impaired phagolysosome maturation in CF.</div><div><h3>Methods</h3><div>To determine the role of macrophage Piezo1 on phagolysosome maturation in CF, we measured phagolysosome maturation ± <em>P. aeruginosa</em> lipopolysaccharide (LPS) (100 ng/mL for 6h, Invivogen) using pHrodo Zymosan particles (Invitrogen) in wild type (WT) and Cftr G542X (Cftr knock-out) bone marrow-derived macrophages (BMDMs). Piezo1 surface expression and Ca<sup>2+</sup> channel activity were measured by flow cytometry and the FLIPR 5 Ca<sup>2+</sup> Assay (Molecular Devices), respectively. To determine the effect of Piezo1 on <em>P. aeruginosa</em> lung infection <em>in vivo</em>, we administered a CF clinical strain of <em>P. aeruginosa</em> (PAM 57-15) to Piezo1<sup>fl/fl</sup> (Piezo1 sufficient) and Piezo1<sup>LysMCre</sup> (Piezo1 myeloid depleted) mice and measured bacterial clearance and bronchoalveolar lavage cell count and differential. To translate our findings to human CF, we performed an Ingenuity pathway analysis on published 10X genomic RNA sequencing data using airway macrophages from healthy and CF expectorated sputum [1]. Finally, Piezo1 mRNA was measured from healthy control (HC) and CF peripheral blood mononuclear cells (PBMCs).</div></div><div>To determine the role of macrophage Piezo1 on phagolysosome maturation in CF, we measured phagolyso","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 45"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 17Helicity and membrane permeabilization do not predict human cathelicidin activity against Pseudomonas aeruginosa","authors":"J. Albin, B. Pentelute","doi":"10.1016/j.jcf.2026.07.049","DOIUrl":"10.1016/j.jcf.2026.07.049","url":null,"abstract":"<div><h3>Background</h3><div>The human host defense peptide LL-37 other cathelicidin derivatives are thought to require helical structure to achieve membrane permeabilization, which in turn leads to gram-negative cell death. In our prior work, however, we have identified both cathelicidin variants that kill <em>Escherichia coli</em> without permeabilizing and strains of <em>P. aeruginosa</em> from people with cystic fibrosis that are permeabilized without being killed[1,2]. Using a short cathelicidin scaffold derived in the course of our work on cathelicidin-based therapeutics, we set out here to better understand the relationships among cathelicidin helicity, membrane permeabilization, and gram-negative killing using a paired helix scanning method to directly interrogate the mechanistic consequences of the sidechain-independent modulation of peptide helical content.</div></div><div>The human host defense peptide LL-37 other cathelicidin derivatives are thought to require helical structure to achieve membrane permeabilization, which in turn leads to gram-negative cell death. In our prior work, however, we have identified both cathelicidin variants that kill <em>Escherichia coli</em> without permeabilizing and strains of <em>P. aeruginosa</em> from people with cystic fibrosis that are permeabilized without being killed[1,2]. Using a short cathelicidin scaffold derived in the course of our work on cathelicidin-based therapeutics, we set out here to better understand the relationships among cathelicidin helicity, membrane permeabilization, and gram-negative killing using a paired helix scanning method to directly interrogate the mechanistic consequences of the sidechain-independent modulation of peptide helical content.</div><div><h3>Methods</h3><div>Characterization of intrinsic helical propensity for each peptide was assessed by circular dichroism in 20% trifluoroethanol. Antimicrobial susceptibility was assessed by broth dilution using both <em>E. coli</em> (ATCC 25922) and <em>P. aeruginosa</em> (ATCC 27853). Dual membrane permeabilization assays were carried out using N-phenyl-naphthylamine and propidium iodide as markers of outer and inner membrane permeabilization, respectively.</div></div><div>Characterization of intrinsic helical propensity for each peptide was assessed by circular dichroism in 20% trifluoroethanol. Antimicrobial susceptibility was assessed by broth dilution using both <em>E. coli</em> (ATCC 25922) and <em>P. aeruginosa</em> (ATCC 27853). Dual membrane permeabilization assays were carried out using N-phenyl-naphthylamine and propidium iodide as markers of outer and inner membrane permeabilization, respectively.</div><div><h3>Results</h3><div>Scanning of a short cathelicidin helix using paired alanine (Ala) versus aminoisobutyric acid (Aib) modifications at each position revealed that an overall average fold-change in helicity among Aib derivatives of 3.2, matching an average 3.3-fold increase in antimicrobial activity again","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 8-9"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 69Emerging microbiological gap under CFTR modulator therapy in a pediatric cystic fibrosis center: a longitudinal cohort study","authors":"M. Cestari, L. Parra, L. Arce, P. Guayama, S. Sleiman, A. Tolli, H. Gutierrez","doi":"10.1016/j.jcf.2026.07.101","DOIUrl":"10.1016/j.jcf.2026.07.101","url":null,"abstract":"<div><h3>Background</h3><div>CFTR modulators have transformed the prognosis of cystic fibrosis (CF), yet their impact on respiratory microbiology in Latin American pediatric cohorts with a high proportion of non-eligible genotypes remains undocumented.</div></div><div>CFTR modulators have transformed the prognosis of cystic fibrosis (CF), yet their impact on respiratory microbiology in Latin American pediatric cohorts with a high proportion of non-eligible genotypes remains undocumented.</div><div><h3>Objective</h3><div>To describe respiratory infection trajectories according to CFTR modulator exposure and to assess whether differential access generates a microbiological gap linked to genotype.</div></div><div>To describe respiratory infection trajectories according to CFTR modulator exposure and to assess whether differential access generates a microbiological gap linked to genotype.</div><div><h3>Methods</h3><div>Longitudinal study based on the International Cystic Fibrosis Training Network Registry (ICFTN-R), including 79 patients aged 6 to 17 years (2022–2025): 41 exposed to modulators (modulator group) and 38 unexposed (non-modulator group). A total of 1,246 respiratory cultures were analyzed. Pseudomonas aeruginosa (PsA) infection status was classified according to Leeds criteria. Predicted FEV1% was evaluated stratified by infection and treatment.</div></div><div>Longitudinal study based on the International Cystic Fibrosis Training Network Registry (ICFTN-R), including 79 patients aged 6 to 17 years (2022–2025): 41 exposed to modulators (modulator group) and 38 unexposed (non-modulator group). A total of 1,246 respiratory cultures were analyzed. Pseudomonas aeruginosa (PsA) infection status was classified according to Leeds criteria. Predicted FEV1% was evaluated stratified by infection and treatment.</div><div><h3>Results</h3><div>PsA prevalence declined from 32.1% to 6.1% in the modulator group (scissor pattern), while it increased from 16.0% to 25.0% in the non-modulator group. According to Leeds criteria, chronic infection was eliminated in the modulator group (10.8%→0%) but persisted in the non-modulator group (3.3%). Active infection (chronic + intermittent) decreased by 74% in the modulator group versus 11% in the non-modulator group. FEV1 divergence widened from Δ1.2 pp to Δ14.2 pp by 2025. Patients without F508del (49% of the cohort) had only 23% access to CFTR modulators and a 24% PsA isolation rate.</div></div><div>PsA prevalence declined from 32.1% to 6.1% in the modulator group (scissor pattern), while it increased from 16.0% to 25.0% in the non-modulator group. According to Leeds criteria, chronic infection was eliminated in the modulator group (10.8%→0%) but persisted in the non-modulator group (3.3%). Active infection (chronic + intermittent) decreased by 74% in the modulator group versus 11% in the non-modulator group. FEV1 divergence widened from Δ1.2 pp to Δ14.2 pp by 2025. Patients without F508del (49% of the cohort) h","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 34"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 68Pseudomonas aeruginosa develop faster ciprofloxacin and meropenem resistance in people with cystic fibrosis-related diabetes","authors":"B. Nielsen, H. Nielsen, H. Krogh-Johansen","doi":"10.1016/j.jcf.2026.07.100","DOIUrl":"10.1016/j.jcf.2026.07.100","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic resistance remains a concern in the cystic fibrosis (CF) community. In non-CF populations, type 2 diabetes has been linked to antibiotic resistance development. However, whether CF–related diabetes (CFRD) is associated with antibiotic resistance development in <em>Pseudomonas aeruginosa</em> (PA) among people with CF (pwCF) remains unclear.</div></div><div>Antibiotic resistance remains a concern in the cystic fibrosis (CF) community. In non-CF populations, type 2 diabetes has been linked to antibiotic resistance development. However, whether CF–related diabetes (CFRD) is associated with antibiotic resistance development in <em>Pseudomonas aeruginosa</em> (PA) among people with CF (pwCF) remains unclear.</div><div><h3>Methods</h3><div>We conducted a retrospective observational study of pwCF followed at the Copenhagen CF Center, Denmark, from 2002–2023. Data were aggregated by participant-year and included pwCF with ≥1 HbA1c measurement and ≥1 sputum sample. CFRD was defined as annual mean HbA1c ≥48 mmol/mol and considered permanent thereafter. PA colonization was assessed as the annual proportion of PA-positive sputum samples (0%, >0–25%, >25–50%, >50–75%, >75%) and annual mean semi-quantitative PA growth score (0–1, >1–2, >2–3) among PA-positive samples. Antibiotic resistance was defined as detection of the first resistant isolate. Associations between CFRD and PA colonization were analyzed using generalized linear mixed models adjusted for age, sex, calendar year, and pre-/post-ETI period and accounting for repeated measurements. Time to antibiotic resistance was analyzed using Cox regression with time since first PA detection as the time scale, adjusted for age, annual number of PA-positive samples, and year of first PA detection (2002 or >2002).</div></div><div>We conducted a retrospective observational study of pwCF followed at the Copenhagen CF Center, Denmark, from 2002–2023. Data were aggregated by participant-year and included pwCF with ≥1 HbA1c measurement and ≥1 sputum sample. CFRD was defined as annual mean HbA1c ≥48 mmol/mol and considered permanent thereafter. PA colonization was assessed as the annual proportion of PA-positive sputum samples (0%, >0–25%, >25–50%, >50–75%, >75%) and annual mean semi-quantitative PA growth score (0–1, >1–2, >2–3) among PA-positive samples. Antibiotic resistance was defined as detection of the first resistant isolate. Associations between CFRD and PA colonization were analyzed using generalized linear mixed models adjusted for age, sex, calendar year, and pre-/post-ETI period and accounting for repeated measurements. Time to antibiotic resistance was analyzed using Cox regression with time since first PA detection as the time scale, adjusted for age, annual number of PA-positive samples, and year of first PA detection (2002 or >2002).</div><div><h3>Results</h3><div>Overall, 362 pwCF contributed 4,819 participant-years and","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 33-34"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 3Identification, characterization, and clinical use of bacteriophages against Achromobacter infection in cystic fibrosis","authors":"J. Massey, N. Wallace, K. Hughes Kramer, G. Haidar, D. Van Tyne","doi":"10.1016/j.jcf.2026.07.035","DOIUrl":"10.1016/j.jcf.2026.07.035","url":null,"abstract":"<div><h3>Background</h3><div><em>Achromobacter</em> is a genus of gram-negative bacteria which are clinically relevant as a pulmonary pathogen in persons with cystic fibrosis (pwCF). <em>Achromobacter</em> is prevalent, correlated with negative clinical outcomes, and difficult to manage in pwCF. Due to its intrinsically multidrug-resistant nature and ability to rapidly acquire additional resistance, there are very few treatment options available for pwCF suffering from <em>Achromobacter</em> infection. Thus, <em>Achromobacter </em>is an ideal candidate for the development of new treatment options.</div><div>Bacteriophages (phages) are naturally occurring, ubiquitous viruses that specifically infect and kill bacteria. With the growing antibiotic resistance crisis, there has been newfound interest in utilizing phages to treat bacterial infections. However, there is currently little data surrounding phage therapy for <em>Achromobacter</em> infections. Therefore, we set out to isolate and characterize phages with activity against <em>Achromobacter</em> to evaluate their potential role as a therapeutic agent in pwCF.</div></div><div><em>Achromobacter</em> is a genus of gram-negative bacteria which are clinically relevant as a pulmonary pathogen in persons with cystic fibrosis (pwCF). <em>Achromobacter</em> is prevalent, correlated with negative clinical outcomes, and difficult to manage in pwCF. Due to its intrinsically multidrug-resistant nature and ability to rapidly acquire additional resistance, there are very few treatment options available for pwCF suffering from <em>Achromobacter</em> infection. Thus, <em>Achromobacter </em>is an ideal candidate for the development of new treatment options.</div><div>Bacteriophages (phages) are naturally occurring, ubiquitous viruses that specifically infect and kill bacteria. With the growing antibiotic resistance crisis, there has been newfound interest in utilizing phages to treat bacterial infections. However, there is currently little data surrounding phage therapy for <em>Achromobacter</em> infections. Therefore, we set out to isolate and characterize phages with activity against <em>Achromobacter</em> to evaluate their potential role as a therapeutic agent in pwCF.</div><div><h3>Methods</h3><div>Wastewater samples from environmental sources were filtered and then plated on enriched media with clinical <em>Achromobacter</em> isolates. Individual plaques were passaged, purified, then sequenced to identify and characterize each phage. Concurrently, we gathered clinical isolates of <em>Achromobacter</em> from pwCF at our hospital system, sequenced their genomes, and established a host range of the isolated phages against the clinical <em>Achromobacter</em> isolates. Phage-resistant <em>Achromobacter</em> mutants were generated by growing bacteria in phage-containing medium. Whole-genome sequencing was conducted on phage-resistant mutants to identify mutations associated with phage resistance.</div></div><div","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 2"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 34Bile acids as potential immunomodulatory signals","authors":"S. Durfey, J. Maaskant, J. Moran, I. Miralda, M. Shrestha, H. Ozuna, X. Ji, P. Dawson, J. Chandler, R. Tirouvanziam, B. Kopp","doi":"10.1016/j.jcf.2026.07.066","DOIUrl":"10.1016/j.jcf.2026.07.066","url":null,"abstract":"<div><h3>Background</h3><div>Plasma and sputum from people with CF (pwCF) suppress macrophage functions and it is unknown what induces this suppression. This suppression could be mediated by bile acids (BA), as BA are dysregulated in CF in metabolomic studies of clinical samples and mechanistic studies showing direct CFTR effects on BA regulation. Importantly, some BA species and their derivatives can regulate gut and liver immune cell function by reducing pro-inflammatory cytokine production and phagocytosis. However, it remains unclear whether systemic and airway macrophages respond to BAs, and whether BA dysregulation persists with CFTR modulator therapy.</div></div><div>Plasma and sputum from people with CF (pwCF) suppress macrophage functions and it is unknown what induces this suppression. This suppression could be mediated by bile acids (BA), as BA are dysregulated in CF in metabolomic studies of clinical samples and mechanistic studies showing direct CFTR effects on BA regulation. Importantly, some BA species and their derivatives can regulate gut and liver immune cell function by reducing pro-inflammatory cytokine production and phagocytosis. However, it remains unclear whether systemic and airway macrophages respond to BAs, and whether BA dysregulation persists with CFTR modulator therapy.</div><div><h3>Methods</h3><div>Plasma samples from pwCF pre- and post-elexacaftor/tezacaftor/ivacaftor (ETI) were assessed for BAs and related metabolites. Single-cell RNA sequencing data from the Chan-Zuckerberg CellxGene database were mined to determine if BA receptors are expressed in lung-resident macrophages. Human monocyte-derived macrophages (MDMs) from healthy and CF donors were differentiated with 20% human serum, exposed to BA for 24hrs, and BA effects on phagocytosis and intracellular killing were assessed.</div></div><div>Plasma samples from pwCF pre- and post-elexacaftor/tezacaftor/ivacaftor (ETI) were assessed for BAs and related metabolites. Single-cell RNA sequencing data from the Chan-Zuckerberg CellxGene database were mined to determine if BA receptors are expressed in lung-resident macrophages. Human monocyte-derived macrophages (MDMs) from healthy and CF donors were differentiated with 20% human serum, exposed to BA for 24hrs, and BA effects on phagocytosis and intracellular killing were assessed.</div><div><h3>Results</h3><div>Untargeted metabolomics revealed two BAs in the top 10 most elevated metabolites in CF plasma (vs healthy), and this difference persisted following ETI. We further investigated BA levels using a quantitative panel of 64 BA species. Hyocholic, cholic, and chenodeoxycholic acids were all significantly elevated in plasma from pwCF pre-ETI. This difference persisted with ETI, with a further increase in hyocholic acid. As BA alterations can influence other signaling molecules, such as the production of fatty acids like oxylipins, we also quantified both esterified and non-esterified versions of 50 different oxyli","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 17"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}