Journal of Cystic Fibrosis最新文献

{"title":"Poster: 41Longitudinal bronchoalveolar lavage profiling in cystic fibrosis patients on elexacaftor/tezacaftor/ivacaftor therapy: A multi-modal analysis","authors":"E. Mullen, G. Bateman, D. Quigley, M. Murphy, C. Gunaratnam, M. Casey, G. McElvaney","doi":"10.1016/j.jcf.2026.07.073","DOIUrl":"10.1016/j.jcf.2026.07.073","url":null,"abstract":"<div><h3>Background</h3><div>Highly effective CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has transformed cystic fibrosis (CF) care; however, its long-term effects on airway inflammation, protease-antiprotease balance, and the lung microbiome remain incompletely understood. We aimed to characterise these features using bronchoalveolar lavage (BAL) and paired plasma sampling in CF patients receiving prolonged ETI therapy, compared with non-CF bronchiectasis (NCFB) controls.</div></div><div>Highly effective CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has transformed cystic fibrosis (CF) care; however, its long-term effects on airway inflammation, protease-antiprotease balance, and the lung microbiome remain incompletely understood. We aimed to characterise these features using bronchoalveolar lavage (BAL) and paired plasma sampling in CF patients receiving prolonged ETI therapy, compared with non-CF bronchiectasis (NCFB) controls.</div><div><h3>Methods</h3><div>We performed 90 bronchoscopies, including 50 in CF patients treated with ETI for ≥4 years. A subset of CF participants underwent repeat bronchoscopy one year later, enabling longitudinal analysis. Comparator data were obtained from 20 NCFB patients. BAL sampling was performed from two discrete lobar sites, the medial segment of the right middle lobe and the inferior segment of the lingula with time-matched blood sampling. Inflammatory mediators were analysed using ELISA and activity-based assays and whole genome sequencing was performed to characterise microbial composition, diversity and antimicrobial resistance profiles.</div></div><div>We performed 90 bronchoscopies, including 50 in CF patients treated with ETI for ≥4 years. A subset of CF participants underwent repeat bronchoscopy one year later, enabling longitudinal analysis. Comparator data were obtained from 20 NCFB patients. BAL sampling was performed from two discrete lobar sites, the medial segment of the right middle lobe and the inferior segment of the lingula with time-matched blood sampling. Inflammatory mediators were analysed using ELISA and activity-based assays and whole genome sequencing was performed to characterise microbial composition, diversity and antimicrobial resistance profiles.</div><div><h3>Results</h3><div>CF patients with pseudomonas aeruginosa exhibited significantly higher BAL IL-1β, IL-8, and NE activity compared with ETI treated patients without pseudomonas and NCFB controls. Further there was marked interlobar variation in BAL inflammatory markers observed within individuals. In samples with high NE activity, a dearth of intact AAT and SLPI indicated protease activity exceeding antiprotease capacity. Microbiome analysis demonstrated reduced prevalence of pseudomonas aeruginosa but increased detection of other pathogens, e.g. staphylococcus aureus, haemophilus influenzae and anaerobes, with overall increased pathogen diversity. Greater microbial alpha diversit","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 20-21"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964939","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: 79Genetic and chemical correction of cystic fibrosis transmembrane conductance regulator reduces airway susceptibility to viral infection in an induced pluripotent stem cell derived airway epithelium","authors":"S. Rollins, L. Tavares, A. Hume, D. Chen, R. Yeboah, J. Yin, D. Kotton, B. Levy, M. Saeed, E. Mühlberger, R. Wang","doi":"10.1016/j.jcf.2026.07.111","DOIUrl":"10.1016/j.jcf.2026.07.111","url":null,"abstract":"<div><h3>Background</h3><div>The airway epithelium is a primary target of viral infection and a key regulator of host defense, particularly in cystic fibrosis (CF). Persons with CF (PwCF) experienced disproportionately severe influenza A (IAV) during the 2009 H1N1 pandemic and heterozygous CFTR mutation carriers show increased IAV complications, implicating CFTR-dependent epithelial programs in viral response. In contrast, during the SARS-CoV-2 pandemic, individuals receiving CFTR modulators had unexpectedly milder disease highlighting a gap in understanding how CFTR dysfunction alters viral infectivity, epithelial injury, antiviral responses, and whether CFTR modulation confers protection beyond correction of ion transport. Limited availability of genetically matched, physiologically relevant human models has constrained progress. To address this, we used a patient-specific human induced pluripotent stem cell (iPSC)-derived airway epithelial platform from CF and syngeneic CFTR-corrected controls to interrogate epithelial-intrinsic antiviral responses to IAV and SARS-CoV-2 with and without elexacaftor/tezacaftor/ivacaftor (ETI). We further incorporated an in vivo murine</div></div><div>The airway epithelium is a primary target of viral infection and a key regulator of host defense, particularly in cystic fibrosis (CF). Persons with CF (PwCF) experienced disproportionately severe influenza A (IAV) during the 2009 H1N1 pandemic and heterozygous CFTR mutation carriers show increased IAV complications, implicating CFTR-dependent epithelial programs in viral response. In contrast, during the SARS-CoV-2 pandemic, individuals receiving CFTR modulators had unexpectedly milder disease highlighting a gap in understanding how CFTR dysfunction alters viral infectivity, epithelial injury, antiviral responses, and whether CFTR modulation confers protection beyond correction of ion transport. Limited availability of genetically matched, physiologically relevant human models has constrained progress. To address this, we used a patient-specific human induced pluripotent stem cell (iPSC)-derived airway epithelial platform from CF and syngeneic CFTR-corrected controls to interrogate epithelial-intrinsic antiviral responses to IAV and SARS-CoV-2 with and without elexacaftor/tezacaftor/ivacaftor (ETI). We further incorporated an in vivo murine</div><div><h3>Methods</h3><div>CF and CFTR-corrected iPSC-derived airway epithelia and primary airways were infected with IAV or SARS-CoV-2 ± ETI. Viral burden, epithelial injury, and transcriptional responses were assessed by RT-PCR, single-cell RNA sequencing, immunofluorescence, and histology. In vivo, mice received ETI before or after intranasal IAV infection; weight loss, lung inflammation, viral load, and epithelial injury were evaluated.</div></div><div>CF and CFTR-corrected iPSC-derived airway epithelia and primary airways were infected with IAV or SARS-CoV-2 ± ETI. Viral burden, epithelial injury, and transcriptional r","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 39-40"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964942","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: 65Modeling slow growth reveals antibiotic tolerance mechanisms in Pseudomonas aeruginosa from the CF lung","authors":"R. Hunter, H. Donnelly, M. Bergkessel, N. Thorns","doi":"10.1016/j.jcf.2026.07.097","DOIUrl":"10.1016/j.jcf.2026.07.097","url":null,"abstract":"<div><h3>Background</h3><div>People with cystic fibrosis (pwCF) are often chronically colonised with <em>Pseudomonas aeruginosa</em>. Even with highly effective modulator therapy and antibiotic treatment, infections persist. <em>P. aeruginosa</em> grows slowly within the lungs of pwCF, due in part to limitation for oxygen and metals such as iron or zinc. Slow growth has been suggested to increase antibiotic tolerance, and we hypothesize that slow growth imposed by oxygen and nutrient limitation contributes to antibiotic treatment failure. To examine this hypothesis, we characterized two slow-growth models: a simple <em>in vitro</em> condition incorporating SCFM4 medium [1] and hypoxic conditions; and the previously described DOAC human epithelial cell-<em>P. aeruginosa</em> co-culture system [2]. Here, we evaluated the efficacies of existing antibiotics and screened ∼30,000 compounds for activity against <em>P. aeruginosa</em> to seek novel chemical matter that might exploit distinct vulnerabilities of <em>P. aeruginosa</em> under slow-growing states.</div></div><div>People with cystic fibrosis (pwCF) are often chronically colonised with <em>Pseudomonas aeruginosa</em>. Even with highly effective modulator therapy and antibiotic treatment, infections persist. <em>P. aeruginosa</em> grows slowly within the lungs of pwCF, due in part to limitation for oxygen and metals such as iron or zinc. Slow growth has been suggested to increase antibiotic tolerance, and we hypothesize that slow growth imposed by oxygen and nutrient limitation contributes to antibiotic treatment failure. To examine this hypothesis, we characterized two slow-growth models: a simple <em>in vitro</em> condition incorporating SCFM4 medium [1] and hypoxic conditions; and the previously described DOAC human epithelial cell-<em>P. aeruginosa</em> co-culture system [2]. Here, we evaluated the efficacies of existing antibiotics and screened ∼30,000 compounds for activity against <em>P. aeruginosa</em> to seek novel chemical matter that might exploit distinct vulnerabilities of <em>P. aeruginosa</em> under slow-growing states.</div><div><h3>Methods</h3><div>To assess physiological states of bacteria in our slow-growth models, we carried out bacterial colony-forming unit (CFU) counts over time, measurements of new protein synthesis (using BONCAT [3]), and RNA-Seq. To measure antibacterial efficacy of known antibiotic and novel compounds in high throughput, we used a bacterial outgrowth assay. Briefly, we incubated an <em>oprM</em> (efflux pump) mutant of <em>P. aeruginosa</em> PA01 in our model conditions with test or control compounds for 5 hours. Following this incubation, a small aliquot of the culture was diluted into rich media in a new plate (1:25 dilution). Wells showing at least a 150-minute delay in outgrowth compared to a DMSO-only control were considered as potential hits.</div></div><div>To assess physiological states of bacteria in our slow-growth models, we carried out bacte","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 32"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964990","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: 14Hypochlorite regulates an epoxide-hydrolase virulence circuit in Pseudomonas aeruginosa","authors":"S. He, A. Simard, N. Taher, K. Hvorecny, M. Ragusa, A. Schmoker, A. Hickman, F. Dyda, D. Madden","doi":"10.1016/j.jcf.2026.07.046","DOIUrl":"10.1016/j.jcf.2026.07.046","url":null,"abstract":"<div><h3>Background</h3><div><em>Pseudomonas aeruginosa</em> secretes an epoxide hydrolase Cif into the airway of people with cystic fibrosis (pwCF). Acting as a virulence factor, Cif reduces the cell-surface abundance of CFTR and also triggers hyperinflammation, leading to worse outcomes for pwCF. Cif helps <em>P. aeruginosa</em> detoxify environmental chemicals, and its expression can be triggered by the presence of reactive epoxides. However, the regulation of <em>cif</em> expression in the context of pwCF airway is unknown.</div></div><div><em>Pseudomonas aeruginosa</em> secretes an epoxide hydrolase Cif into the airway of people with cystic fibrosis (pwCF). Acting as a virulence factor, Cif reduces the cell-surface abundance of CFTR and also triggers hyperinflammation, leading to worse outcomes for pwCF. Cif helps <em>P. aeruginosa</em> detoxify environmental chemicals, and its expression can be triggered by the presence of reactive epoxides. However, the regulation of <em>cif</em> expression in the context of pwCF airway is unknown.</div><div><h3>Methods</h3><div>We performed structural studies on CifR, a TetR family transcriptional repressor, which regulates <em>cif</em> expression. Using purified CifR protein and synthetic operator DNA derived from the cif promoter, we conducted a compound library screen to identify chemicals capable of disrupting the CifR–DNA complex. Various biochemical approaches, including mass spectrometry, were applied to reveal the mechanism of regulation by small-molecule compounds.</div></div><div>We performed structural studies on CifR, a TetR family transcriptional repressor, which regulates <em>cif</em> expression. Using purified CifR protein and synthetic operator DNA derived from the cif promoter, we conducted a compound library screen to identify chemicals capable of disrupting the CifR–DNA complex. Various biochemical approaches, including mass spectrometry, were applied to reveal the mechanism of regulation by small-molecule compounds.</div><div><h3>Results</h3><div>We determined high-resolution crystal structures of three forms of CifR: the apo form, operator DNA-bound complex, and an intermediate state obtained in the presence of an epoxide. Comparison of the three structures revealed large conformational shifts, demonstrating how the protein is dynamically remodeled to execute its function. A pivotal residue of this mechanism is Cys107, situated in the ligand-binding domain. The formation of epoxide adducts at Cys107 drives a conformational change that is essential for DNA release. Several electrophilic reactive agents serve as alternative signaling compounds for this virulent circuit. For instance, sodium hypochlorite oxidizes Cys107, disrupts the CifR–DNA complex, and mimics the effect of epoxides, leading to <em>cif</em> expression. These findings show that covalent modification of Cys107 can allosterically switch CifR from a DNA-bound to a DNA-free state, thereby activating the epoxide-hydrolase vi","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 7"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965058","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: 32Staphylococcus aureus infection alters the lung metabolome to promote coinfection with Pseudomonas aeruginosa via homoserine in the cystic fibrosis rat","authors":"K. Shaffer, J. Keith, A. Oden, S. Combs, L. Wilson, S. Barnes, R. Boone, M. Kiedwroski, S. Birket","doi":"10.1016/j.jcf.2026.07.064","DOIUrl":"10.1016/j.jcf.2026.07.064","url":null,"abstract":"<div><h3>Background</h3><div>Cystic fibrosis (CF) lung disease is characterized by the accumulation of mucus, inflammation, and polymicrobial infections that lead to lung function decline. <em>Staphylococcus aureus</em> (<em>Sa</em>) is the primary pathogen isolated from the lungs of children and young adults with CF and is replaced as the predominant microbe by <em>Pseudomonas aeruginosa</em> (<em>Pa</em>) as patients age. Coinfection with <em>Sa</em> and <em>Pa</em> is common and causes worse clinical outcomes. Data from our lab has demonstrated that infection with <em>Sa</em> promotes coinfection with both clinical and environmental strains of <em>Pa</em>. Additionally, we have found that <em>Sa</em> infection alters the CF lung metabolome. We hypothesize that <em>Sa</em> infection primes the CF lung for <em>Pa</em> infection by altering the lung metabolome and increasing levels of homoserine.</div></div><div>Cystic fibrosis (CF) lung disease is characterized by the accumulation of mucus, inflammation, and polymicrobial infections that lead to lung function decline. <em>Staphylococcus aureus</em> (<em>Sa</em>) is the primary pathogen isolated from the lungs of children and young adults with CF and is replaced as the predominant microbe by <em>Pseudomonas aeruginosa</em> (<em>Pa</em>) as patients age. Coinfection with <em>Sa</em> and <em>Pa</em> is common and causes worse clinical outcomes. Data from our lab has demonstrated that infection with <em>Sa</em> promotes coinfection with both clinical and environmental strains of <em>Pa</em>. Additionally, we have found that <em>Sa</em> infection alters the CF lung metabolome. We hypothesize that <em>Sa</em> infection primes the CF lung for <em>Pa</em> infection by altering the lung metabolome and increasing levels of homoserine.</div><div><h3>Methods</h3><div>Our lab developed a CFTR knockout rat (CF rat) that recapitulates the lung disease of people with CF. WT and CF rats were singly or dually infected with 10<sup>7</sup> CFUs of <em>Sa</em> and/or <em>Pa</em> in agarose beads via intratracheal instillation following 24hr growth in synthetic CF sputum medium (SCFM) with or without 100μM supplemental homoserine. Animals were sacrificed at 7-, 14- or 21-days post-infection. Bronchoalveolar lavage fluid (BALF) was collected, and nutrient availability was assessed via untargeted metabolomics. BALF was also used to quantify immune cell infiltration and cytokine levels were measured with ELISA kits. Lung tissue was homogenized and plated for CFUs. Recovered <em>Pa</em> isolates as well as <em>Pa</em> grown with 100μM homoserine for 24hr were sent for whole genome sequencing and variant calling analysis. In vitro growth curves were performed using a microplate reader that measured the OD<sub>600</sub> every 20min for 24hr. A USA300 <em>Sa</em> mutant lacking homoserine dehydrogenase (Δ<em>hsd</em>) was obtained from the Nebraska Transposon Mutant Library and was used to create a Δ<em>hsd</em> mutant in o","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 16"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965060","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: 51Evolution of Staphylococcus aureus during chronic infection in people with cystic fibrosis","authors":"C. Bianco, P. Planet","doi":"10.1016/j.jcf.2026.07.083","DOIUrl":"10.1016/j.jcf.2026.07.083","url":null,"abstract":"<div><h3>Background</h3><div>Cystic fibrosis (CF) affects over 105,000 individuals and is characterized by chronic pulmonary infections driving morbidity and mortality [1]. <em>Staphylococcus aureus</em> is the most frequently isolated respiratory pathogen in CF patients [2]. Early colonization is associated with chronic infection, airway inflammation and lung function decline [3]. However, mechanisms of long-term <em>S. aureus</em> persistence and adaptation remain poorly understood. Prior studies show genetic and phenotypic adaptation during chronic infection, including antibiotic resistance and small colony variants [4], but comprehensive genomic analyses remain limited. Whole-genome sequencing enables investigation of persistence, transmission, and adaptive evolution.</div></div><div>Cystic fibrosis (CF) affects over 105,000 individuals and is characterized by chronic pulmonary infections driving morbidity and mortality [1]. <em>Staphylococcus aureus</em> is the most frequently isolated respiratory pathogen in CF patients [2]. Early colonization is associated with chronic infection, airway inflammation and lung function decline [3]. However, mechanisms of long-term <em>S. aureus</em> persistence and adaptation remain poorly understood. Prior studies show genetic and phenotypic adaptation during chronic infection, including antibiotic resistance and small colony variants [4], but comprehensive genomic analyses remain limited. Whole-genome sequencing enables investigation of persistence, transmission, and adaptive evolution.</div><div><h3>Methods</h3><div>We analyzed 105 <em>S. aureus</em> genomes from 42 people with CF (2009–2011). Phylogenomics defined clonal relationships, persistence, and transmission. Within-host evolution was assessed using core genome alignments and ancestral reconstruction to identify single nucleotide polymorphisms (SNPs).</div></div><div>We analyzed 105 <em>S. aureus</em> genomes from 42 people with CF (2009–2011). Phylogenomics defined clonal relationships, persistence, and transmission. Within-host evolution was assessed using core genome alignments and ancestral reconstruction to identify single nucleotide polymorphisms (SNPs).</div><div><h3>Results</h3><div>In several individuals, a single clonal lineage persisted over extended periods, while others were infected by multiple strains. We identified 23 strain-sharing events suggesting potential transmission. Clonal complex 5 (CC5) predominated, contrasting with CC8 dominance in non-CF populations. A high burden of antibiotic resistance was observed, including widespread β-lactam resistance and frequent fluoroquinolone resistance; 34% of isolates carried dual <em>gyrA/grlA</em> mutations associated with high-level resistance, and 33% were methicillin-resistant. Longitudinal analyses showed within-host evolution consistent with substitution rates (∼10<sup>-6</sup> substitutions/site/year). Adaptive mutations were identified in genes involved in metabolism, stress resp","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 25"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965062","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: 74Association of gene expression of the transcription factor WhiB7 with phenotypic heterogeneity in Mycobacterium abscessus cystic fibrosis clinical isolates","authors":"J. Corley, J. Congel, K. Haist, K. Malcolm, F. Jia, V. Calado Nogueira de Moura, J. Nick, K. Hisert","doi":"10.1016/j.jcf.2026.07.106","DOIUrl":"10.1016/j.jcf.2026.07.106","url":null,"abstract":"<div><h3>Background</h3><div><em>Mycobacterium abscessus</em> (<em>Mabsc</em>) pulmonary infection is a complication in people with cystic fibrosis (pwCF), contributing to progressive lung function decline, airway inflammation, and poor treatment outcomes. Further, <em>Mabsc</em> infections are clinically heterogeneous, ranging from apparently indolent colonization to progressive, active disease. This variability likely reflects differences in the host airway environment, intrinsic genetic diversity among bacterial isolates, and stress-induced bacterial gene expression pathways that promote survival and persistence. Prior work demonstrated that <em>Mabsc</em> WhiB7, a stress-responsive transcription factor, is induced by ribosome targeting anti-pseudomonal antibiotic tobramycin, promoting <em>Mabsc</em> survival during host-relevant conditions, within human macrophages, and in murine infections. Because <em>whiB7</em> is induced by multiple factors that target the bacterial ribosome, its expression likely varies depending on the presence and quantities of inducers. Previous whole genome sequencing (WGS) of 246 <em>Mabsc</em> clinical isolates from pwCF, collected through cohorts including the PREDICT and PATIENCE studies, revealed conservation of <em>whiB7</em>, with only a single non-synonymous mutation identified. This finding suggests strong selective pressure to maintain WhiB7 function during infection. Although <em>whiB7</em> is highly conserved across isolates, we hypothesize that its expression is heterogeneous in vivo, and that this variability contributes to differing infection outcomes ranging from indolent colonization to progressive, inflammatory disease.</div></div><div><em>Mycobacterium abscessus</em> (<em>Mabsc</em>) pulmonary infection is a complication in people with cystic fibrosis (pwCF), contributing to progressive lung function decline, airway inflammation, and poor treatment outcomes. Further, <em>Mabsc</em> infections are clinically heterogeneous, ranging from apparently indolent colonization to progressive, active disease. This variability likely reflects differences in the host airway environment, intrinsic genetic diversity among bacterial isolates, and stress-induced bacterial gene expression pathways that promote survival and persistence. Prior work demonstrated that <em>Mabsc</em> WhiB7, a stress-responsive transcription factor, is induced by ribosome targeting anti-pseudomonal antibiotic tobramycin, promoting <em>Mabsc</em> survival during host-relevant conditions, within human macrophages, and in murine infections. Because <em>whiB7</em> is induced by multiple factors that target the bacterial ribosome, its expression likely varies depending on the presence and quantities of inducers. Previous whole genome sequencing (WGS) of 246 <em>Mabsc</em> clinical isolates from pwCF, collected through cohorts including the PREDICT and PATIENCE studies, revealed conservation of <em>whiB7</em>, with only a single non-synonymous ","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 37-38"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964691","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: 76Persistent positive cultures for Mycobacterium abscessus in cystic fibrosis does not reflect genomic divergence or enhanced virulence","authors":"T. Koch, M. Teve, V. Calado Nogueira de Moura, B. Vestal, L. Ding, J. Nick, J. Honda","doi":"10.1016/j.jcf.2026.07.108","DOIUrl":"10.1016/j.jcf.2026.07.108","url":null,"abstract":"<div><h3>Background</h3><div><em>Mycobacterium abscessus</em> (MABS) is a highly drug-resistant pathogen in cystic fibrosis (CF), associated with chronic infection and accelerated lung function decline. A subset of people with CF (pwCF) show persistent positive cultures despite prolonged multidrug therapy, raising the concept of a “persister” phenotype. Yet, whether persistence reflects true bacterial evolution, enhanced virulence, or phenotypic adaptation is poorly defined. We investigated the biological basis of MABS persistence in CF by comparing longitudinal isolates across pre-treatment and persistent (post-treatment) states, integrating genomic, phenotypic, and host-pathogen interaction analyses.</div></div><div><em>Mycobacterium abscessus</em> (MABS) is a highly drug-resistant pathogen in cystic fibrosis (CF), associated with chronic infection and accelerated lung function decline. A subset of people with CF (pwCF) show persistent positive cultures despite prolonged multidrug therapy, raising the concept of a “persister” phenotype. Yet, whether persistence reflects true bacterial evolution, enhanced virulence, or phenotypic adaptation is poorly defined. We investigated the biological basis of MABS persistence in CF by comparing longitudinal isolates across pre-treatment and persistent (post-treatment) states, integrating genomic, phenotypic, and host-pathogen interaction analyses.</div><div><h3>Methods</h3><div>56 longitudinal CF isolates were categorized as indolent, pre-treatment, or persistent (post-treatment). Whole genome phylogenetic analysis assessed genetic divergence. Phenotypic profiling included morphological classification, growth kinetics, and biofilm formation with antibiotic susceptibility testing. Host-pathogen interactions were evaluated using primary alveolar macrophages and monocyte-derived macrophages from CF & non-CF donors, measuring uptake, intracellular survival, replication, and TNFα. DualRNAseq was performed on infected macrophages from healthy donors at 24hrs post-infection to assess host and bacterial transcriptional responses.</div></div><div>56 longitudinal CF isolates were categorized as indolent, pre-treatment, or persistent (post-treatment). Whole genome phylogenetic analysis assessed genetic divergence. Phenotypic profiling included morphological classification, growth kinetics, and biofilm formation with antibiotic susceptibility testing. Host-pathogen interactions were evaluated using primary alveolar macrophages and monocyte-derived macrophages from CF & non-CF donors, measuring uptake, intracellular survival, replication, and TNFα. DualRNAseq was performed on infected macrophages from healthy donors at 24hrs post-infection to assess host and bacterial transcriptional responses.</div><div><h3>Results</h3><div>Phylogenetic analysis revealed high genomic similarity within longitudinal isolates, with no evidence of genetic divergence in pre-treatment vs. persistent strains. Rough morphotypes were m","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 38-39"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964693","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: 61The effect of highly effective modulator therapy on incidence of viral infections in pulmonary exacerbations in cystic fibrosis","authors":"K. Sevier, N. Robertson, M. Phillips, S. Patel, K. Psoter, C. Merlo, R. Dezube, N. Lechtzin, K. Montemayor, N. West","doi":"10.1016/j.jcf.2026.07.093","DOIUrl":"10.1016/j.jcf.2026.07.093","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary exacerbations (PEx) occur frequently in people with cystic fibrosis (pwCF) and are associated with decreased lung function. Viral associated PEx have a greater decline in lung function. This study examines incidence of viral infections and changes in lung function, comparing two cohorts before and after the majority of pwCF were eligible for highly effective modulator therapy (HEMT).</div></div><div>Pulmonary exacerbations (PEx) occur frequently in people with cystic fibrosis (pwCF) and are associated with decreased lung function. Viral associated PEx have a greater decline in lung function. This study examines incidence of viral infections and changes in lung function, comparing two cohorts before and after the majority of pwCF were eligible for highly effective modulator therapy (HEMT).</div><div><h3>Methods</h3><div>A retrospective cohort study conducted in pwCF ≥18 years at Johns Hopkins from 2013-2018 (Cohort 1: before widespread availability of HEMT) and 2020-2025 (Cohort 2: after HEMT), admitted to the hospital for treatment for PEx. Exposure defined as a positive respiratory viral panel (RVP), collected at time of PEx. Lung function as measured as ppFEV1 was collected: highest in the past 12 months (baseline), at the start and end of IV treatment, and 3-month follow-up. Primary outcomes: change in ppFEV1 from baseline to each time point and return to 90% baseline ppFEV1. Generalized estimating equations-based regression models were used to evaluate the association of presence of a respiratory viral infection and outcomes.</div></div><div>A retrospective cohort study conducted in pwCF ≥18 years at Johns Hopkins from 2013-2018 (Cohort 1: before widespread availability of HEMT) and 2020-2025 (Cohort 2: after HEMT), admitted to the hospital for treatment for PEx. Exposure defined as a positive respiratory viral panel (RVP), collected at time of PEx. Lung function as measured as ppFEV1 was collected: highest in the past 12 months (baseline), at the start and end of IV treatment, and 3-month follow-up. Primary outcomes: change in ppFEV1 from baseline to each time point and return to 90% baseline ppFEV1. Generalized estimating equations-based regression models were used to evaluate the association of presence of a respiratory viral infection and outcomes.</div><div><h3>Results</h3><div>287 pwCF were included overall with 3.9 (mean=4.0) PEx requiring hospitalization. Mean age at first PEx was 31.3 (SD=12.8) years, 152 (53.0%) were female, 254 (88.5%) were Caucasian, 140 (48.8%) were homozygous for F508del. 157 (22.7%) were on a CFTR modulator in Cohort 1, and 204 (65.0%) in Cohort 2 (p< 0.001). 1,006 PEx with RVP results were identified (692 in Cohort 1, and 314 in Cohort 2). Overall, 198 (17.8%) PEx were associated with a positive RVP, with no significant difference between cohorts (Cohort 1: 127 (18.4%), Cohort 2: 71 (16.8%) positive for a virus, p=0.57).</div><div>Table 1: Of 692 PEx in Cohort 1, 127 (","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 30"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964748","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: 82Airway microbiome dynamics preceding incident nontuberculous mycobacterial infection in cystic fibrosis","authors":"L. Carmody, B. Wagner, M. Zimbric, E. Hanley, S. Martiniano, J. Harris, L. Caverly","doi":"10.1016/j.jcf.2026.07.114","DOIUrl":"10.1016/j.jcf.2026.07.114","url":null,"abstract":"<div><h3>Background</h3><div>Nontuberculous mycobacterial (NTM) infections in people with CF (pwCF) can lead to clinical decline and NTM pulmonary disease. As NTM infections remain prevalent in CF, novel strategies are needed to identify modifiable NTM risk factors. Prior work has suggested airway microbiome as a potential determinant of NTM infection in CF. This study aimed to identify microbial features of CF airway samples that are predictive NTM infection.</div></div><div>Nontuberculous mycobacterial (NTM) infections in people with CF (pwCF) can lead to clinical decline and NTM pulmonary disease. As NTM infections remain prevalent in CF, novel strategies are needed to identify modifiable NTM risk factors. Prior work has suggested airway microbiome as a potential determinant of NTM infection in CF. This study aimed to identify microbial features of CF airway samples that are predictive NTM infection.</div><div><h3>Methods</h3><div>Longitudinal sputum and oropharyngeal (OP) swab samples collected from pwCF were obtained from biorepositories at the University of Michigan (UM) and Children’s Hospital Colorado (CHCO). An NTM positive cohort was matched to NTM-negative controls on age, calendar year, and FEV<sub>1</sub>. Included samples were collected within two years prior to incident NTM infection (or matched NTM negative culture date for controls). Bacterial prevalence and relative abundances were determined from 16S rRNA gene sequencing, and total bacterial load was quantified. Alpha (Shannon diversity, evenness) and beta (Morisita-Horn (MH) index) diversity metrics were derived from community profiles. For each sample type, microbial features were compared between NTM and control groups. Mixed models were fit to microbial features, including site as a covariate for total bacterial load. Global community structures were compared between sample types and sites with principal component analysis (PCA) and permutational multivariate analysis of variance (PERMANOVA). Within each site, differential abundance analyses were performed to identify differences in taxa prevalence and abundance between NTM and control groups.</div></div><div>Longitudinal sputum and oropharyngeal (OP) swab samples collected from pwCF were obtained from biorepositories at the University of Michigan (UM) and Children’s Hospital Colorado (CHCO). An NTM positive cohort was matched to NTM-negative controls on age, calendar year, and FEV<sub>1</sub>. Included samples were collected within two years prior to incident NTM infection (or matched NTM negative culture date for controls). Bacterial prevalence and relative abundances were determined from 16S rRNA gene sequencing, and total bacterial load was quantified. Alpha (Shannon diversity, evenness) and beta (Morisita-Horn (MH) index) diversity metrics were derived from community profiles. For each sample type, microbial features were compared between NTM and control groups. Mixed models were fit to microbial features, including si","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 41-42"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964753","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}