Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 73, Issue 8, Pages 2054-2063Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dky144
Keywords
-
Funding
- National Research Foundation of Korea (NRF) grant - Korean Government [2016R1A2A1A05005440]
- Global Research Laboratory (GRL) grant [NRF-2014K1A1A2064460]
- National Research Foundation of Korea [22A20130012098, 2014K1A1A2064460, 2016R1A2A1A05005440] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Objectives: The worldwide increase in antibiotic-resistant bacteria is a growing threat to public health. Antimicrobial peptides (AMPs) are potentially effective alternatives to conventional antibiotics. We therefore tested analogues of the AMP mBjAMP1 from Branchiostoma japonicum, which we produced by adding and/or replacing amino acids to increase antimicrobial activity against Gram-negative bacteria. Methods: We compared the antimicrobial activities of mBjAMP1 analogues against Gram-negative bacteria reference strains and 52 strains of Klebsiella pneumoniae isolated from patients. Antibiofilm activity and cytotoxicity were evaluated, and the mechanisms of action were then studied. Results: Analogue peptides exhibited greater antimicrobial and antibiofilm activities than mBjAMP1. In particular, the analogue IARR-Anal10 displayed not only the greatest antimicrobial and antibiofilm activities, but also no toxicity against human red blood cells or other mammalian cells. IARR-Anal10 had little or no effect on bacterial outer membrane permeability, membrane polarization or membrane integrity. Instead, it appears IARR-Anal10 binds bacterial DNS, as evidenced in DNA gel retardation assays. Thus, IARR-Anal10 likely kills bacteria through an intracellular mechanism. We also confirmed that IARR-Anal10 suppresses the virulence of K. pneumoniae to a degree similar to tigecycline, used to treat carbapenem-resistant Enterobacteriaceae infections. Notably, IARR-Anal10 did not induce development of resistance by K. pneumoniae, though both meropenem and tigecycline did so within a short time. Conclusions: These results suggest that IARR-Anal10 is a promising agent for treating infections caused by teria resistant to tigecycline and meropenem.
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