Abstract

There are no wholly successful chemotherapeutic strategies against Burkholderia cepacia complex (BCC) colonization in cystic fibrosis (CF). We assessed the impact of cysteamine (Lynovex) in combination with standard-of-care CF antibiotics in vitro against BCC CF isolates by the concentration at which 100% of bacteria were killed (MIC100) and checkerboard assays under CLSI standard conditions. Cysteamine facilitated the aminoglycoside-, fluoroquinolone- and folate pathway inhibitor-mediated killing of BCC organisms that were otherwise resistant or intermediately sensitive to these antibiotic classes. Slow-growing BCC strains are often recalcitrant to treatment and form biofilms. In assessing the impact of cysteamine on biofilms, we demonstrated inhibition of BCC biofilm formation at sub-MIC100s of cysteamine.

Highlights

  • There are no wholly successful chemotherapeutic strategies against Burkholderia cepacia complex (BCC) colonization in cystic fibrosis (CF)

  • We previously described the antimicrobial, antibiofilm, and mucolytic attributes of cysteamine against Pseudomonas aeruginosa and other CF bacterial pathogens [10,11,12] and report here that, more strikingly, the modification of currently available therapeutic strategies [2, 13] with the introduction of cysteamine as an adjunct antimicrobial agent brings about effective killing of BCC

  • The 36 Burkholderia strains employed for this study include representative strains from each species, including B. cenocepacia and B. multivorans, those most commonly associated with infection in cystic fibrosis [14]

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Summary

Introduction

There are no wholly successful chemotherapeutic strategies against Burkholderia cepacia complex (BCC) colonization in cystic fibrosis (CF). If not all, BCC strains [5] are clinically resistant or inherently insensitive to currently available CF antibiotics [2, 6, 7]. We previously described the antimicrobial, antibiofilm, and mucolytic attributes of cysteamine against Pseudomonas aeruginosa and other CF bacterial pathogens [10,11,12] and report here that, more strikingly, the modification of currently available therapeutic strategies [2, 13] with the introduction of cysteamine as an adjunct antimicrobial agent brings about effective killing of BCC (both type strains and CF isolates)

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