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Elucidation of the mechanism behind the potentiating activity of baicalin against Burkholderia cenocepacia biofilms

Lisa Slachmuylders (UGent) , Heleen Van Acker (UGent) , Gilles Brackman (UGent) , Andrea Sass (UGent) , Filip Van Nieuwerburgh (UGent) and Tom Coenye (UGent)
(2018) PLOS ONE. 13(1).
Author
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Abstract
Reduced antimicrobial susceptibility due to resistance and tolerance has become a serious threat to human health. An approach to overcome this reduced susceptibility is the use of antibiotic adjuvants, also known as potentiators. These are compounds that have little or no antibacterial effect on their own but increase the susceptibility of bacterial cells towards antimicrobial agents. Baicalin hydrate, previously described as a quorum sensing inhibitor, is such a potentiator that increases the susceptibility of Burkholderia cenocepacia J2315 biofilms towards tobramycin. The goal of the present study is to elucidate the molecular mechanisms behind the potentiating activity of baicalin hydrate and related flavonoids. We first determined the effect of multiple flavonoids on susceptibility of B. cenocepacia J2315 towards tobramycin. Increased antibiotic susceptibility was most pronounced in combination with apigenin 7-O-glucoside and baicalin hydrate. For baicalin hydrate, also other B. cepacia complex strains and other antibiotics were tested. The potentiating effect was only observed for aminoglycosides and was both strain- and aminoglycoside-dependent. Subsequently, gene expression was compared between baicalin hydrate treated and untreated cells, in the presence and absence of tobramycin. This revealed that baicalin hydrate affected cellular respiration, resulting in increased reactive oxygen species production in the presence of tobramycin. We subsequently showed that baicalin hydrate has an impact on oxidative stress via several pathways including oxidative phosphorylation, glucarate metabolism and by modulating biosynthesis of putrescine. Furthermore, our data strongly suggest that the influence of baicalin hydrate on oxidative stress is unrelated to quorum sensing. Our data indicate that the potentiating effect of baicalin hydrate is due to modulating the oxidative stress response, which in turn leads to increased tobramycin-mediated killing.
Keywords
BURKHOLDERIA-CEPACIA COMPLEX, QUORUM-SENSING INHIBITORS, BACTERICIDAL, ANTIBIOTICS, PSEUDOMONAS-AERUGINOSA, ESCHERICHIA-COLI, OXIDATIVE STRESS, CYSTIC-FIBROSIS, RESISTANCE, VIRULENCE, POLYAMINES

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Citation

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MLA
Slachmuylders, Lisa et al. “Elucidation of the Mechanism Behind the Potentiating Activity of Baicalin Against Burkholderia Cenocepacia Biofilms.” PLOS ONE 13.1 (2018): n. pag. Print.
APA
Slachmuylders, L., Van Acker, H., Brackman, G., Sass, A., Van Nieuwerburgh, F., & Coenye, T. (2018). Elucidation of the mechanism behind the potentiating activity of baicalin against Burkholderia cenocepacia biofilms. PLOS ONE, 13(1).
Chicago author-date
Slachmuylders, Lisa, Heleen Van Acker, Gilles Brackman, Andrea Sass, Filip Van Nieuwerburgh, and Tom Coenye. 2018. “Elucidation of the Mechanism Behind the Potentiating Activity of Baicalin Against Burkholderia Cenocepacia Biofilms.” Plos One 13 (1).
Chicago author-date (all authors)
Slachmuylders, Lisa, Heleen Van Acker, Gilles Brackman, Andrea Sass, Filip Van Nieuwerburgh, and Tom Coenye. 2018. “Elucidation of the Mechanism Behind the Potentiating Activity of Baicalin Against Burkholderia Cenocepacia Biofilms.” Plos One 13 (1).
Vancouver
1.
Slachmuylders L, Van Acker H, Brackman G, Sass A, Van Nieuwerburgh F, Coenye T. Elucidation of the mechanism behind the potentiating activity of baicalin against Burkholderia cenocepacia biofilms. PLOS ONE. 2018;13(1).
IEEE
[1]
L. Slachmuylders, H. Van Acker, G. Brackman, A. Sass, F. Van Nieuwerburgh, and T. Coenye, “Elucidation of the mechanism behind the potentiating activity of baicalin against Burkholderia cenocepacia biofilms,” PLOS ONE, vol. 13, no. 1, 2018.
@article{8551241,
  abstract     = {Reduced antimicrobial susceptibility due to resistance and tolerance has become a serious threat to human health. An approach to overcome this reduced susceptibility is the use of antibiotic adjuvants, also known as potentiators. These are compounds that have little or no antibacterial effect on their own but increase the susceptibility of bacterial cells towards antimicrobial agents. Baicalin hydrate, previously described as a quorum sensing inhibitor, is such a potentiator that increases the susceptibility of Burkholderia cenocepacia J2315 biofilms towards tobramycin. The goal of the present study is to elucidate the molecular mechanisms behind the potentiating activity of baicalin hydrate and related flavonoids. We first determined the effect of multiple flavonoids on susceptibility of B. cenocepacia J2315 towards tobramycin. Increased antibiotic susceptibility was most pronounced in combination with apigenin 7-O-glucoside and baicalin hydrate. For baicalin hydrate, also other B. cepacia complex strains and other antibiotics were tested. The potentiating effect was only observed for aminoglycosides and was both strain- and aminoglycoside-dependent. Subsequently, gene expression was compared between baicalin hydrate treated and untreated cells, in the presence and absence of tobramycin. This revealed that baicalin hydrate affected cellular respiration, resulting in increased reactive oxygen species production in the presence of tobramycin. We subsequently showed that baicalin hydrate has an impact on oxidative stress via several pathways including oxidative phosphorylation, glucarate metabolism and by modulating biosynthesis of putrescine. Furthermore, our data strongly suggest that the influence of baicalin hydrate on oxidative stress is unrelated to quorum sensing. Our data indicate that the potentiating effect of baicalin hydrate is due to modulating the oxidative stress response, which in turn leads to increased tobramycin-mediated killing.},
  articleno    = {e0190533},
  author       = {Slachmuylders, Lisa and Van Acker, Heleen and Brackman, Gilles and Sass, Andrea and Van Nieuwerburgh, Filip and Coenye, Tom},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {BURKHOLDERIA-CEPACIA COMPLEX,QUORUM-SENSING INHIBITORS,BACTERICIDAL,ANTIBIOTICS,PSEUDOMONAS-AERUGINOSA,ESCHERICHIA-COLI,OXIDATIVE STRESS,CYSTIC-FIBROSIS,RESISTANCE,VIRULENCE,POLYAMINES},
  language     = {eng},
  number       = {1},
  pages        = {18},
  title        = {Elucidation of the mechanism behind the potentiating activity of baicalin against Burkholderia cenocepacia biofilms},
  url          = {http://dx.doi.org/10.1371/journal.pone.0190533},
  volume       = {13},
  year         = {2018},
}

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