Document Detail


Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets.
MedLine Citation:
PMID:  24074402     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic bacterial lung infections in cystic fibrosis (CF) are caused by defects in the CF transmembrane conductance regulator chloride channel. Previously, we described that newborn CF transmembrane conductance regulator-knockout ferrets rapidly develop lung infections within the first week of life. Here, we report a more slowly progressing lung bacterial colonization phenotype observed in juvenile to adult CF ferrets reared on a layered antibiotic regimen. Even on antibiotics, CF ferrets were still very susceptible to bacterial lung infection. The severity of lung histopathology ranged from mild to severe, and variably included mucus obstruction of the airways and submucosal glands, air trapping, atelectasis, bronchopneumonia, and interstitial pneumonia. In all CF lungs, significant numbers of bacteria were detected and impaired tracheal mucociliary clearance was observed. Although Streptococcus, Staphylococcus, and Enterococcus were observed most frequently in the lungs of CF animals, each animal displayed a predominant bacterial species that accounted for over 50% of the culturable bacteria, with no one bacterial taxon predominating in all animals. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry fingerprinting was used to quantify lung bacteria in 10 CF animals and demonstrated Streptococcus, Staphylococcus, Enterococcus, or Escherichia as the most abundant genera. Interestingly, there was significant overlap in the types of bacteria observed in the lung and intestine of a given CF animal, including bacterial taxa unique to the lung and gut of each CF animal analyzed. These findings demonstrate that CF ferrets develop lung disease during the juvenile and adult stages that is similar to patients with CF, and suggest that enteric bacterial flora may seed the lung of CF ferrets.
Authors:
Xingshen Sun; Alicia K Olivier; Bo Liang; Yaling Yi; Hongshu Sui; Turan I A Evans; Yulong Zhang; Weihong Zhou; Scott R Tyler; John T Fisher; Nicholas W Keiser; Xiaoming Liu; Ziying Yan; Yi Song; J Adam Goeken; Joann M Kinyon; Danielle Fligg; Xiaoyan Wang; Weiliang Xie; Thomas J Lynch; Paul M Kaminsky; Zoe A Stewart; R Marshall Pope; Timothy Frana; David K Meyerholz; Kalpaj Parekh; John F Engelhardt
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  50     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-03-04     Completed Date:  2014-04-24     Revised Date:  2014-07-09    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  502-12     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Animals, Genetically Modified
Anti-Bacterial Agents / administration & dosage
Bacterial Translocation*
Cystic Fibrosis / drug therapy,  genetics,  metabolism,  microbiology*,  physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator / deficiency*,  genetics
Disease Models, Animal
Disease Progression
Ferrets / genetics,  metabolism*
Genetic Predisposition to Disease
Intestines / drug effects,  microbiology*
Lung / drug effects,  metabolism,  microbiology*,  physiopathology
Mucociliary Clearance
Phenotype
Respiratory Tract Infections / drug therapy,  genetics,  metabolism,  microbiology*,  physiopathology
Grant Support
ID/Acronym/Agency:
DK047967/DK/NIDDK NIH HHS; DK054759/DK/NIDDK NIH HHS; HL091842/HL/NHLBI NIH HHS; HL108902/HL/NHLBI NIH HHS; K08 DK092284/DK/NIDDK NIH HHS; K08 DK092284/DK/NIDDK NIH HHS; K08 HL114725/HL/NHLBI NIH HHS; K08 HL114725/HL/NHLBI NIH HHS; P30 ES005605/ES/NIEHS NIH HHS; R37 DK047967/DK/NIDDK NIH HHS; T32 GM007337/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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