Susceptibility of Pseudomonas aeruginosa biofilm to alpha-helical peptides: D-enantiomer of LL-37

被引:119
作者
Dean, Scott N. [1 ]
Bishop, Barney M. [2 ]
van Hoek, Monique L. [3 ,4 ]
机构
[1] George Mason Univ, Dept Biol, Manassas, VA 20110 USA
[2] George Mason Univ, Dept Chem & Biochem, Manassas, VA 20110 USA
[3] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA
[4] George Mason Univ, Natl Ctr Biodefense & Infect Dis, Manassas, VA 20110 USA
来源
FRONTIERS IN MICROBIOLOGY | 2011年 / 2卷
关键词
Pseudomonas; biofilm; cathelicidin; enantiomer; mimetic; protease-resistance; chiral;
D O I
10.3389/fmicb.2011.00128
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Pseudomonas aeruginosa is a highly versatile opportunistic pathogen and its ability to produce biofilms is a direct impediment to the healing of wounds and recovery from infection. Interest in anti-microbial peptides (AMPs) has grown due to their potential therapeutic applications and their possible use against antibiotic resistant bacteria. LL-37 is the only cathelicidin expressed by humans. In this study, we tested LL-37 and the effect of a protease-resistant LL-37 peptide mimetic, the peptide enantiomer D-LL-37, for anti-microbial and anti-biofilm activity against P aeruginosa. Both forms of the peptide were equally effective as AMPs with similar killing kinetics. Circular dichroism spectra were obtained to demonstrate the chirality of D- and L-LL-37, and the trypsin resistance of D-LL-37 was confirmed. The helical cathelicidin from the cobra Naja atra (NA-CATH), and synthetic peptide variations (ATRA-1, ATRA-2, NA-CATH:ATRA1-ATRA1) were also tested. Although the cobra cathelicidin and related peptides had strong anti-microbial activity, those tested did not inhibit Pseudomonas biofilm formation, neither did control peptides. Both D- and L-LL-37 inhibited the attachment of Pseudomonas to a 96-well plate and decreased the amount of pre-formed (established) biofilm. D-LL-37 is able to promote Pseudomonas motility and decrease biofilm formation by altering the rate of twitching as well as by downregulating the expression of the biofilm-related genes, rhIA and rhIB, similar to L-LL-37. Both L- and D-LL-37 protected Galleria mellonella in vivo against Pseudomonas infection, while NA-CATH:ATRA1-ATRA1 peptide did not. This study demonstrates the ability and equivalence of D-LL-37 compared to L-LL-37 to promote bacterial twitching motility and inhibit biofilm formation, and protect against in vivo infection, and suggests that this peptide could be a critical advancement in the development of new treatments for P aeruginosa infection.
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页数:11
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