J. Turner et al., ACTIVITIES OF LL-37, A CATHELIN-ASSOCIATED ANTIMICROBIAL PEPTIDE OF HUMAN NEUTROPHILS, Antimicrobial agents and chemotherapy, 42(9), 1998, pp. 2206-2214
Human neutrophils contain two structurally distinct types of antimicro
bial peptides, P-sheet defensins (HNP-1 to HNP-4) and the alpha-helica
l peptide LL-37, We used radial diffusion assays and an improved Natio
nal Committee for Clinical Laboratory Standards-type broth microdiluti
on assay to compare the antimicrobial properties of LL-37, HNP-1, and
protegrin (PG-1), Although generally less potent than PC-1, LL-37 show
ed considerable activity (MIC, <10 mu g/ml) against Pseudomonas aerugi
nosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes
, Staphylococcus epidermidis, Staphylococcus aureus, and vancomycin-re
sistant enterococci, even in media that contained 100 mM NaCl, Certain
organisms (methicillin resistant S, aureus, Proteus mirabilis, and Ca
ndida albicans) were resistant to LL-37 in media that contained 100 mM
NaCl but were susceptible in low-salt media. Burkholderia cepacia was
resistant to LL-37, PC-1, and HNP-1 in low- or high-salt media. LL-37
caused outer and inner membrane permeabilization of E. coli ML-35p. C
hromogenic Limulus assays revealed that LL-37 bound to E, coli O111:B4
lipopolysaccharide (LPS) with a high affinity and that this binding s
howed positive cooperativity (Hill coefficient = 2.02), Circular dichr
oism spectrometry disclosed that LL-37 underwent conformational change
in the presence of lipid A, transitioning from a random coil to an al
pha-helical structure, The broad-spectrum antimicrobial properties of
LL-37, its presence in neutrophils, and its inducibility in keratinocy
tes all suggest that this peptide and its precursor (hCAP-18) may prot
ect skin and other tissues from bacterial intrusions and LPS-induced t
oxicity. The potent activity of LL-37 against P. aeruginosa, including
mucoid and antibiotic-resistant strains, suggests that it or related
molecules might have utility as topical bronchopulmonary microbicides
in cystic fibrosis.