Abstract

Pseudomonas aeruginosa is the most prevalent bacterial species that contribute to cystic fibrosis (CF) respiratory failure. The impaired function of CF transmembrane conductance regulator leads to abnormal epithelial Cl–/HCO3– transport and acidification of airway surface liquid. However, it remains unclear why the CF lung is most commonly infected by Pseudomonas aeruginosa versus other pathogens. We carried out studies to investigate if lower pH helps Pseudomonas aeruginosa adapt and thrive in the CF-like acidic lung environment. Our results revealed that Pseudomonas aeruginosa generally forms more biofilm, induces antibiotic resistance faster in acidic conditions, and can be reversed by returning the acidic environment to physiologically neutral conditions. Pseudomonas aeruginosa appears to be highly adaptive to the CF-like acidic pH environment. By studying the effects of an acidic environment on bacterial response, we may provide a new therapeutic option in preventing chronic Pseudomonas aeruginosa infection and colonization.

Highlights

  • Cystic fibrosis (CF) is a genetic disease involving compromised function of cystic fibrosis transmembrane conductance regulator (CFTR) that leads to impaired airway host defense and causes lung inflammation and bacterial infections (Pezzulo et al, 2012; Shah et al, 2016)

  • Pseudomonas aeruginosa gradually increases its presence in the CF airways after the pathological phenotypes of CFTR malfunction appear more obviously with the increased age of the CF sufferers (Cystic Fibrosis Foundation, 2020)

  • We first examined the effects of salt concentration and acidic condition on bacterial planktonic and biofilm mode of growth to understand the effects of the CF-like microenvironment on the behavior of P. aeruginosa

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Summary

Introduction

Cystic fibrosis (CF) is a genetic disease involving compromised function of cystic fibrosis transmembrane conductance regulator (CFTR) that leads to impaired airway host defense and causes lung inflammation and bacterial infections (Pezzulo et al, 2012; Shah et al, 2016). The prevalence of P. aeruginosa lung infection gradually increases over time from approximately 20% to 70% in CF patients from age 2 to 45 (Cystic Fibrosis Foundation, 2020), which coincides with an increase in CF disease severity. Bacteria expand their population in the natural environment and the host via two different forms.

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