Abstract
Multidrug-resistant Acinetobacter baumannii has recently emerged as an important pathogen in nosocomial infection; thus, effective antimicrobial regimens are urgently needed. Human antimicrobial peptides (AMPs) exhibit multiple functions and antimicrobial activities against bacteria and fungi and are proposed to be potential adjuvant therapeutic agents. This study examined the effect of the human cathelicidin-derived AMP LL-37 on A. baumannii and revealed the underlying mode of action. We found that LL-37 killed A. baumannii efficiently and reduced cell motility and adhesion. The bacteria-killing effect of LL-37 on A. baumannii was more efficient compared to other AMPs, including human ß–defensin 3 (hBD3) and histatin 5 (Hst5). Both flow cytometric analysis and immunofluorescence staining showed that LL-37 bound to A. baumannii cells. Moreover, far-western analysis demonstrated that LL-37 could bind to the A. baumannii OmpA (AbOmpA) protein. An ELISA assay indicated that biotin-labelled LL-37 (BA-LL37) bound to the AbOmpA74-84 peptide in a dose-dependent manner. Using BA-LL37 as a probe, the ~38 kDa OmpA signal was detected in the wild type but the ompA deletion strain did not show the protein, thereby validating the interaction. Finally, we found that the ompA deletion mutant was more sensitive to LL-37 and decreased cell adhesion by 32% compared to the wild type. However, ompA deletion mutant showed a greatly reduced adhesion defect after LL-37 treatment compared to the wild strain. Taken together, this study provides evidence that LL-37 affects A. baumannii through OmpA binding.
Highlights
Antimicrobial peptides (AMPs) are generated by a wide variety of organisms as a part of the host defense
These results indicate that LL-37 exhibits bactericidal activity against A. baumannii
LL-37 is an important component of the human innate immune defense [5,37]
Summary
Antimicrobial peptides (AMPs) are generated by a wide variety of organisms as a part of the host defense. AMPs are generally short (10–100 amino acids), positively charged (normally +2 to +9) and amphiphilic [3]. AMPs can be divided into three major classes based on their gross amino acid composition and certain structural features, including. OmpA Binding-Dependent Effect of LL-37 on A. baumannii linear alpha-helical peptides (without cysteines), cysteine-containing peptides linked by disulfide bonds and peptides with a high ratio of specific amino acids [2]. Human defensins belong to the second class, and histatins are members of the third class. HCAP-18 (the only member of the cathelicidin AMP family in humans) contains an N-terminal domain, a cathelin domain and a C-terminal LL-37 domain [4]. LL-37 is extracellularly cleaved from hCAP-18 by proteinase 3 and belongs to the class of linear alpha peptides. LL-37 owes its name to the fact that it consists of 37 amino acids that begin with two leucine residues [5]
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