Definition of sinonasal and otologic exacerbation in patients with primary ciliary dyskinesia - an expert consensus DOI Creative Commons
Myrofora Goutaki, Yin Ting Lam, Andreas Anagiotos

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 9, 2024

Abstract Background Recurrent infections of the nose, sinuses, and ears are common problems for people with primary ciliary dyskinesia (PCD). While pulmonary exacerbations in PCD defined, there is no definition Ear-Nose-Throat (ENT) exacerbations, a potential outcome research clinical trials. Methods We set up an expert panel 24 ENT specialists, respiratory physicians, other healthcare professionals, patients to develop consensus definitions sinonasal otologic children adults settings. reviewed literature used modified Delphi approach four electronic surveys. Results Both based on combination major minor criteria, requiring three or two at least criteria each. Major exacerbation are: 1) reported acute increase nasal discharge change colour; 2) pain sensitivity sinus regions; 3) mucopurulent examination. Minor include: symptoms; examination signs; doctoŕs decision treat; improvement after 14-days. ear sensitivity, discharge, examination, 4) signs otitis media otoscopy. hearing problems; complication; treat. Conclusion These might offer useful measure different They should be validated future studies trials together outcomes, assess their usability.

Язык: Английский

Emerging models to study competitive interactions within bacterial communities DOI Creative Commons
Mollie Virgo, Serge Mostowy, Brian T. Ho

и другие.

Trends in Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Within both abiotic and host environments, bacteria typically exist as diverse, multispecies communities have crucial roles in human health, agriculture, industry. In these communities, compete for resources, competitive interactions can shape the overall population structure community function. Studying bacterial dynamics requires experimental model systems that capture different interaction networks between their surroundings. We examine recent literature advancing such systems, including (i) silico models establishing theoretical basis how cell-to-cell influence level dynamics, (ii) vitro characterizing specific interbacterial interactions, (iii) organ-on-a-chip revealing physiologically relevant parameters, spatial mechanical forces, encounter within a host, (iv) vivo plant animal connecting responses to interactions. Each of has greatly contributed our understanding be used synergistically understand competition influences architecture.

Язык: Английский

Процитировано

1

Biofilm antimicrobial susceptibility through an experimental evolutionary lens DOI Creative Commons
Tom Coenye, Mona Bové, Thomas Bjarnsholt

и другие.

npj Biofilms and Microbiomes, Год журнала: 2022, Номер 8(1)

Опубликована: Окт. 18, 2022

Abstract Experimental evolution experiments in which bacterial populations are repeatedly exposed to an antimicrobial treatment, and examination of the genotype phenotype resulting evolved bacteria, can help shed light on mechanisms behind reduced susceptibility. In this review we present overview why it is important include biofilms experimental evolution, approaches available study what has taught us about tolerance resistance biofilms. Finally, emerging consensus view biofilm susceptibility supported by data obtained during studies.

Язык: Английский

Процитировано

32

The structure–function relationship ofPseudomonas aeruginosain infections and its influence on the microenvironment DOI Creative Commons
Mads Lichtenberg, Tim Holm Jakobsen, Michael Kühl

и другие.

FEMS Microbiology Reviews, Год журнала: 2022, Номер 46(5)

Опубликована: Апрель 24, 2022

Pseudomonas aeruginosa is a human pathogen associated with both acute and chronic infections. While intensively studied, the basic mechanisms enabling long-term survival of P. in host, despite massive immune system attack heavy antimicrobial treatment, remain to be identified. We argue that such infections may represent niche invasions by influence microenvironment depleting host-derived substrate activating response. Bacteria embedded cell aggregates establish microenvironmental niche, where they endure initial host response slowing down their metabolism. This provides stable, lasting growth conditions constant, albeit slow supply electron acceptors. Under stable conditions, exhibits distinct adaptive traits, its gene expression pattern reflects life exposed continuous antimicrobials. Here, we review fundamental aspects examine how structural organization influences vivo microenvironment, which turn affects interaction biofilm system. discuss improving our knowledge about ecology can used combat persistent, hard-to-treat bacterial

Язык: Английский

Процитировано

28

Microevolution of Pseudomonas aeruginosa in the airways of people with cystic fibrosis DOI Open Access
Nina Cramer,

Jens Klockgether,

Burkhard Tümmler

и другие.

Current Opinion in Immunology, Год журнала: 2023, Номер 83, С. 102328 - 102328

Опубликована: Апрель 26, 2023

Язык: Английский

Процитировано

17

Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells DOI Creative Commons
Paula F. Zamora,

Thomas G. Reidy,

Catherine R. Armbruster

и другие.

PLoS Biology, Год журнала: 2024, Номер 22(4), С. e3002566 - e3002566

Опубликована: Апрель 23, 2024

Phage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there scarce data regarding effects on human host. Here, we aimed understand how phages interact with cells of airway epithelium, tissue site colonized by bacterial biofilms numerous chronic respiratory disorders. Using panel Pseudomonas aeruginosa and epithelial (AECs) derived from person cystic fibrosis (CF), determined interactions between depend specific phage properties well physiochemical features microenvironment. Although poor at internalizing phages, epithelium responds exposure changing transcriptional profile secreting antiviral proinflammatory cytokines correlate families. Overall, our findings indicate mammalian responses are heterogenous could potentially alter way local defenses aid clearance during therapy. Thus, besides receptor specificity particular isolate, criteria select should be expanded include cell responses.

Язык: Английский

Процитировано

5

Iron bioavailability regulates Pseudomonas aeruginosa interspecies interactions through type VI secretion expression DOI Creative Commons
Allison L Haas, Anna C. Zemke, Jeffrey A. Melvin

и другие.

Cell Reports, Год журнала: 2023, Номер 42(3), С. 112270 - 112270

Опубликована: Март 1, 2023

The cystic fibrosis (CF) respiratory tract harbors pathogenic bacteria that cause life-threatening chronic infections. Of these, Pseudomonas aeruginosa becomes increasingly dominant with age and is associated worsening lung function declining microbial diversity. We aimed to understand why P. dominates over other pathogens disease. Here, we show responds dynamic changes in iron concentration, often viral infection pulmonary exacerbations, become more competitive via expression of the TseT toxic effector. However, this behavior can be therapeutically targeted using chelator deferiprone block competition. Overall, find concentration significantly correlate diversity people CF. These findings improve our understanding how CF provide a targetable pathway help prevent shift.

Язык: Английский

Процитировано

11

Cystic fibrosis pathogens persist in the upper respiratory tract following initiation of elexacaftor/tezacaftor/ivacaftor therapy DOI Creative Commons
Yasmin Hilliam, Catherine R. Armbruster, Glenn J. Rapsinski

и другие.

Microbiology Spectrum, Год журнала: 2024, Номер 12(8)

Опубликована: Июнь 25, 2024

ABSTRACT Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but effects on sinus microbiota are still unknown. Changes to airway in CF associated with disease state and alterations bacterial community after ETI initiation may require changes clinical management regimens. We collected swab samples from middle meatus an observational study 38 adults chronic rhinosinusitis (CRS) 2017 2021 captured therapy. performed 16S custom amplicon sequencing characterize pre- post-ETI. Real-time quantitative PCR (RT-qPCR) was estimate total abundance. Sinus people (pwCF) clustered into three types, dependent dominant organism: a Pseudomonas -dominant, Staphylococcus mixed dominance cluster. Shannon’s diversity index low not significantly altered Total load lowered spp. abundance reduced post-ETI, eradication observed. became organism post-ETI we showed presence methicillin-resistant aureus (MRSA) both also demonstrated that microbiome is predictive spp., Serratia sputum. including MRSA, persist sinuses pwCF therapy, indicating these pathogens will continue be important era highly effective modulator therapies (HEMT). IMPORTANCE Highly (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), have patient care quality life individuals. The airways unclear, though work already been published Our presents evidence relative following show becomes communities this cohort identified post-therapy. These findings demonstrate pathogen monitoring remain vital part HEMT.

Язык: Английский

Процитировано

4

Metabolic specialization drives reduced pathogenicity in Pseudomonas aeruginosa isolates from cystic fibrosis patients DOI Creative Commons
Bjarke H. Pedersen, Filipa B. Simões, Ivan Pogrebnyakov

и другие.

PLoS Biology, Год журнала: 2024, Номер 22(8), С. e3002781 - e3002781

Опубликована: Авг. 23, 2024

Metabolism provides the foundation for all cellular functions. During persistent infections, in adapted pathogenic bacteria metabolism functions radically differently compared with more naïve strains. Whether this is simply a necessary accommodation to persistence phenotype or if plays direct role achieving host still unclear. Here, we characterize convergent shift metabolic function(s) linked during Pseudomonas aeruginosa colonization airways of people cystic fibrosis. We show that clinically relevant mutations key enzyme, pyruvate dehydrogenase, lead host-specialized together lower virulence and immune response recruitment. These changes infection are mediated by impaired type III secretion system activity antioxidant metabolite, pyruvate, respectively. Our results how adaptations directly impinge on pathogenicity organism.

Язык: Английский

Процитировано

4

Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection DOI
Lucas A. Meirelles, Evangelia Vayena,

Auriane Debache

и другие.

Nature Microbiology, Год журнала: 2024, Номер 9(12), С. 3284 - 3303

Опубликована: Окт. 25, 2024

Язык: Английский

Процитировано

4

Elexacaftor–Tezacaftor–Ivacaftor Improves Sinonasal Outcomes in Young Children With Cystic Fibrosis DOI Creative Commons
Amanda L. Stapleton, Adam J. Kimple, Jennifer L. Goralski

и другие.

International Forum of Allergy & Rhinology, Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

ABSTRACT Background Severe chronic rhinosinusitis (CRS) is a near universal manifestation of cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor (ETI) an oral, small molecule, highly effective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector–potentiator drug. In people with fibrosis age > 12 years, ETI improves sinonasal symptoms, endoscopy findings, polyp size, and radiologic findings. This study evaluates changes in CRS children ages 6–12 years newly started on ETI. Methods was prospective, three center, pre–post 11 6–11 Study endpoints included the SN‐5 health survey, Sniffin’ Kids olfaction test, sinus computerized tomography (CT) scan, nasal mucus sampling for full‐length 16S rRNA sequencing microbiome analysis. visits were conducted before at median 9 months after treatment initiation. Results lead to improvement scores findings CRS. Olfaction below normal baseline did not improve. The dominated by typically commensal organisms most participants. Additionally, Staphylococcus aureus found five participants six treatment. Conclusions symptoms age. improve this group, suggesting that olfactory dysfunction associated CF established early life. younger cohort pediatric patients presented abundant only very rare Pseudomonas aeruginosa or

Язык: Английский

Процитировано

0