Journal
NATURE MICROBIOLOGY
Volume 3, Issue 6, Pages 718-731Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41564-018-0164-0
Keywords
-
Categories
Funding
- Hungarian Academy of Sciences
- Hungarian Scientific Research Fund [NKFI PD 116222]
- NKFI [120220]
- OTKA PD [109572]
- NKFI FK [124254]
- 'Lendulet' Programme of the Hungarian Academy of Sciences
- Wellcome Trust
- European Research Council [H2020-ERC-2014-CoG 648364, GINOP-2.3.2-15-2016-00014, GINOP-2.3.2-15-2016-00020, GINOP-2.3.3-15-2016-00001]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences
- Boehringer Ingelheim Fonds
Ask authors/readers for more resources
Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available