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Transformation of human cathelicidin LL-37 into selective, stable, and potent antimicrobial compounds.

Abstract：

:This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide prevented staphylococcal biofilm formation in a mouse model of catheter-associated infection. Meanwhile, it boosted the innate immune response to further combat the infection. Because these peptides are potent, cell-selective, and stable to several proteases, they may be utilized to combat one or more ESKAPE pathogens.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Wang G,Hanke ML,Mishra B,Lushnikova T,Heim CE,Chittezham Thomas V,Bayles KW,Kielian T

doi

10.1021/cb500475y

subject

Has Abstract

pub_date

2014-09-19 00:00:00

pages

1997-2002

issue

9

eissn

1554-8929

issn

1554-8937

journal_volume

9

pub_type

信件

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