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Abstract

Cystic fibrosis (CF) is a genetic disorder affecting epithelial ion transport, which among other impacts results in defective mucociliary clearance and innate defenses in the respiratory tract. Consequently, people with CF experience lifelong infections of the respiratory mucosa that are chronic and polymicrobial in nature. Young children with CF are initially colonized by opportunists like nontypeable (NTHi), which normally resides within the microbiome of the nasopharynx and upper airways and can also cause infections of the respiratory mucosa that include bronchitis and otitis media. NTHi is typically supplanted by other microbes as patients age; for example, people with CF are often chronically infected with mucoid strains of , which prior work in our laboratory has shown to promote colonization and persistence by other opportunists that include . Our previous work has shown that polymicrobial infection impacts host colonization and persistence of incoming microbes via diverse mechanisms that include priming of host immunity that can promote microbial clearance, and cooperativity within polymicrobial biofilms, which can promote persistence. In infection studies with BALB/c Cftr mice, results showed, as previously observed for WT BALB/c mice, preceding infection with NTHi decreased colonization and persistence by . Likewise, polymicrobial infection of BALB/c Cftr and C57BL/6 Cftr(FABPhCFTR)1Jaw/J mice showed correlation between and , with increased bacterial colonization and lung pathology. Based on these results, we conclude that our previous observations regarding polymicrobial infections with CF opportunists in WT mice are also validated using CF mice.

Funding
This study was supported by the:
  • National Institute of Diabetes and Digestive and Kidney Diseases (Award P30DK072482)
    • Principle Award Recipient: NotApplicable
  • National Heart, Lung, and Blood Institute (Award T32HL134640)
    • Principle Award Recipient: W.Edward Swords
  • Cystic Fibrosis Foundation (Award RDP R15RO)
    • Principle Award Recipient: NotApplicable
  • Cystic Fibrosis Foundation (Award CFF SWORDS20G0)
    • Principle Award Recipient: W.Edward Swords
  • Cystic Fibrosis Foundation (Award CFF SWORDS1810)
    • Principle Award Recipient: W.Edward Swords
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License
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2023-01-25
2024-05-17
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