Format

Send to

Choose Destination
Chem Biol. 2015 Feb 19;22(2):196-205. doi: 10.1016/j.chembiol.2015.01.002.

D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections.

Author information

1
Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
2
Faculty of Science and Technology, Athabasca University, Athabasca, AB T9S 3A3, Canada.
3
Laboratory of Pharmaceutical Microbiology, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
4
Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: bob@hancocklab.com.

Erratum in

  • Chem Biol. 2015 Sep 17;22(9):1280-2.

Abstract

In many infections, bacteria form surface-associated communities known as biofilms that are substantially more resistant to antibiotics than their planktonic counterparts. Based on the design features of active antibiofilm peptides, we made a series of related 12-amino acid L-, D- and retro-inverso derivatives. Specific D-enantiomeric peptides were the most potent at inhibiting biofilm development and eradicating preformed biofilms of seven species of wild-type and multiply antibiotic-resistant Gram-negative pathogens. Moreover, these peptides showed strong synergy with conventional antibiotics, reducing the antibiotic concentrations required for complete biofilm inhibition by up to 64-fold. As shown previously for 1018, these D-amino acid peptides targeted the intracellular stringent response signal (p)ppGpp. The most potent peptides DJK-5 and DJK-6 protected invertebrates from lethal Pseudomonas aeruginosa infections and were considerably more active than a previously described L-amino acid peptide 1018. Thus, the protease-resistant peptides produced here were more effective both in vitro and in vivo.

PMID:
25699603
PMCID:
PMC4362967
DOI:
10.1016/j.chembiol.2015.01.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center