Clinical impact of Pseudomonas aeruginosa colonization in patients with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare disease causing motile cilia dysfunction, recurrent airway infection, and bronchiectasis. Airway infection management strategies are borrowed from cystic fibrosis. The aim of this study is to describe the management of airway infection with Pseudomonas aeruginosa ( PA) in children and adults with PCD across European centers. An online survey questionnaire was sent electronically using SurveyMonkey® to 55 PCD centers in 36 European countries. Fifty-two responded from 43 centers in 26 countries, a response rate of 70%. Most (89%) countries did not have written guidelines for PCD management. Airway sampling for infection detection at each clinic visit was more likely when follow-up was frequent. Eighty-seven percent of centers chose to treat the first PA isolate, most prescribing combined oral ciprofloxacin and inhaled colistimethate sodium (43%, n = 18). The preferred treatment for chronic infection with PA was nebulized colistimethate in 51% ( n = 22). In summary, considerable variation exists across European centers in the frequency of patient follow-up and airway sampling for infection, treatment goals, and the management of PA infection. Few centers had written guidelines for PCD management. Clinical trials to determine optimal treatment of PA in PCD patients are urgently needed.

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Inactivation of Chibby affects function of motile airway cilia

The Journal of Cell Biology ◽

10.1083/jcb.200809144 ◽

2009 ◽

Vol 185 (2) ◽

pp. 225-233 ◽

Cited By ~ 64

Author(s):

Vera A. Voronina ◽

Ken-Ichi Takemaru ◽

Piper Treuting ◽

Damon Love ◽

Barbara R. Grubb ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Weight Loss ◽

Basal Body ◽

Primary Ciliary Dyskinesia ◽

Apical Surface ◽

Mucociliary Transport ◽

Multiciliated Cells ◽

Activation Of Transcription ◽

Airway Cilia ◽

Ciliary Dyskinesia

Chibby (Cby) is a conserved component of the Wnt–β-catenin pathway. Cby physically interacts with β-catenin to repress its activation of transcription. To elucidate the function of Cby in vertebrates, we generated Cby−/− mice and found that after 2–3 d of weight loss, the majority of mice die before or around weaning. All Cby−/− mice develop rhinitis and sinusitis. When challenged with Pseudomonas aeruginosa isolates, Cby−/− mice are unable to clear the bacteria from the nasal cavity. Notably, Cby−/− mice exhibit a complete absence of mucociliary transport caused by a marked paucity of motile cilia in the nasal epithelium. Moreover, ultrastructural experiments reveal impaired basal body docking to the apical surface of multiciliated cells. In support of these phenotypes, endogenous Cby protein is localized at the base of cilia. As the phenotypes of Cby−/− mice bear striking similarities to primary ciliary dyskinesia, Cby−/− mice may prove to be a useful model for this condition.

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Targeting Pseudomonas aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential

International Journal of Molecular Sciences ◽

10.3390/ijms21010069 ◽

2019 ◽

Vol 21 (1) ◽

pp. 69 ◽

Cited By ~ 2

Author(s):

Giuseppantonio Maisetta ◽

Lucia Grassi ◽

Semih Esin ◽

Esingül Kaya ◽

Andrea Morelli ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Primary Ciliary Dyskinesia ◽

Ethylenediaminetetraacetic Acid ◽

Therapeutic Potential ◽

Ex Vivo ◽

Bacterial Species ◽

Clinical Prognosis ◽

Airway Infections ◽

Ciliary Dyskinesia

In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.

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