«Nanoglobular and linear antimicrobials against biofilms formed by Burkholderia cepacia isolated from cystic fibrosis patients»


Background. Biofilm formation is a major factor contributing to the chronicity of infections. Most patients with cystic fibrosis are chronically infected with Burkholderia cepacia that, once established, is impossible to eradicate and is associated with major morbidity. Established biofilms display high resistance to antimicrobials, and so finding ways to disrupt biofilms is a critical goal in combatting these infections. The aim of the present study was to compare the antibiofilm effect of selected antimicrobials with either linear or compact globular structures.

Methods. In order to study the antibiofilm activity of selected antimicrobials, clinical isolates of B. cepacia from cystic fibrosis patients were used. We tested two antimicrobial agents, linear chlorhexidine (CHG, C22H30Cl2N10) and nanoglobular Mul-1867 (С426H852N204 * 60 HCl), that is 8-10-nm spherical particles, as measured by dynamic light scattering. We then performed a time-kill test to determine the total number of colony forming units in pre-formed, 24-hr old biofilms treated for 60 s with either CHG or Mul-1867 at concentrations that were 100 times their minimum inhibitory concentration using standard microbial techniques. All assays included a minimum of 3 replicates and were repeated in 3 independent experiments.

Results. Both CHG and Mul-1867 were found to display antimicrobial activity. Treatment with CHG reduced the number of B. cepacia in biofilms by 1.8 ± 0.4 log10/mL, whereas treatment with Mul-1867 decreased viable counts by 4.6 ± 0.5 log10/mL (both measured after 60 s of exposure).

Conclusions. Our study demonstrated that a nanoglobular antimicrobial possesses greater antibiofilm activity than a linear one. Both CHG and Mul-1867 are surface-active agents. Thus, the greater antibacterial effect of the nanoglobular antimicrobial may be because it penetrated the surface of the biofilm more effectively than the linear antimicrobial. This work provides insight into the potential to develop nanotechnology products that can destroy B. cepacia biofilms, a major cause of morbidity in chronic infections like cystic fibrosis model, and thus raise the possibility for using this drug as a potential new therapeutic intervention.