2019 ; Vol.29-11: 1707~1716
|Author||Kkabi Son, Jieun Kim, Mihee Jang, Anil Kumar Chauhan, Yangmee Kim|
|Place of duty||Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea|
|Title||Effects of C-Terminal Residues of 12-Mer Peptides on Antibacterial Efficacy and Mechanism|
J. Microbiol. Biotechnol.2019 ;
|Abstract||The development of new antimicrobial agents is essential for the effective treatment of
diseases such as sepsis. We previously developed a new short peptide, Pap12-6, using the 12
N-terminal residues of papiliocin, which showed potent and effective antimicrobial activity
against multidrug-resistant Gram-negative bacteria. Here, we investigated the antimicrobial
mechanism of Pap12-6 and a newly designed peptide, Pap12-7, in which the 12th Trp residue of
Pap12-6 was replaced with Val to develop a potent peptide with high bacterial selectivity and
a different antibacterial mechanism. Both peptides showed high antimicrobial activity against
Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. In addition,
the two peptides showed similar anti-inflammatory activity against lipopolysaccharidestimulated
RAW 264.7 cells, but Pap12-7 showed very low toxicities against sheep red blood
cells and mammalian cells compared to that showed by Pap12-6. A calcein dye leakage assay,
membrane depolarization, and confocal microscopy observations revealed that the two
peptides with one single amino acid change have different mechanisms of antibacterial action:
Pap12-6 directly targets the bacterial cell membrane, whereas Pap12-7 appears to penetrate the
bacterial cell membrane and exert its activities in the cell. The therapeutic efficacy of Pap12-7
was further examined in a mouse model of sepsis, which increased the survival rate of septic
mice. For the first time, we showed that both peptides showed anti-septic activity by reducing
the infiltration of neutrophils and the production of inflammatory factors. Overall, these
results indicate Pap12-7 as a novel non-toxic peptide with potent antibacterial and anti-septic
activities via penetrating the cell membrane.|
|Key_word||Antimicrobial peptide, bacterial cell selectivity, anti-inflammation, antibacterial mechanism, sepsis|
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