Easy Strategy To Increase Salt Resistance of Antimicrobial Peptides

Yu, Huiyuan; Tu, Chih‐Hsiung; Yip, Bak-Sau; Chen, Heng-Li; Cheng, Hsi-Tsung; Huang, Kuo-Chun; Lo, Hsiu‐Jung; Cheng, Jya‐Wei

doi:10.1128/aac.00202-11

Cited by 105 publications

(108 citation statements)

References 22 publications

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“…Moreover, similar to other antimicrobial peptides, antimicrobial potency of P-113 becomes significantly compromised in biological fluid such as plasma, serum, saliva and sputum [22,[29][30][31]. Previously, we have successfully increased salt resistance of antimicrobial peptides by replacing tryptophan or histidine residues with the bulky amino acids b-naphthylalanine and b-(4,4 0 -biphenyl)alanine [32]. The variant, Nal-P-113, with b-naphthylalanine substitution, retained bactericidal activity even at high salt concentration [32].…”

Section: Introductionmentioning

confidence: 96%

“…Previously, we have successfully increased salt resistance of antimicrobial peptides by replacing tryptophan or histidine residues with the bulky amino acids b-naphthylalanine and b-(4,4 0 -biphenyl)alanine [32]. The variant, Nal-P-113, with b-naphthylalanine substitution, retained bactericidal activity even at high salt concentration [32].…”

Section: Introductionmentioning

confidence: 98%

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Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states

Wang

Cheng

et al. 2015

Acta Biomaterialia

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states

Wang

Cheng

et al. 2015

Acta Biomaterialia

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“…2A). In addition, a previous study indicated that P-113 loses its bactericidal activity at pH 4.5 (14). Therefore, the pH sensitivities of the peptides were examined.…”

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confidence: 99%

The Antimicrobial Peptides P-113Du and P-113Tri Function against Candida albicans

Lin

Chen

Xue

et al. 2016

Antimicrob Agents Chemother

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Two antimicrobial P-113 peptide derivatives, P-113Du and P-113Tri, were investigated in this study. Notably, P-113Du and P-113Tri contained significant fractions of ␣-helix conformation and were less sensitive to high salt and low pH than P-113. Moreover, compared to P-113, these peptides exhibited increased antifungal activity against planktonic cells, biofilm cells, and clinical isolates of Candida albicans and non-albicans Candida spp. These results suggest that P-113Du and P-113Tri are promising candidates for development as novel antifungal agents. Histatin 5 (Hst5) is a potent antimicrobial peptide (AMP) with activity against Candida albicans (1). A 12-mer amino acid fragment of Hst5, P-113, retains strong candidacidal activity compared to the parental Hst5 and has had no adverse effects in clinical trials (2-6). P-113 forms an amphipathic ␣-helix in trifluoroethanol, which mimics the hydrophobic environment of microbial membranes (7). However, the interaction between AMPs and microbial membranes is salt sensitive (8, 9). The efficacy of P-113 is significantly reduced in the presence of high salt concentrations, such as 150 mM sodium chloride or 100 mM sodium phosphate (4, 10).To improve the activity of P-113, our approach was based on the dimerization of histatin-derived peptides to increase bactericidal activity against Staphylococcus aureus (11). In this study, the duplicated and triplicated P-113 (designated P-113Du and P-113Tri, respectively) ( Table 1) were characterized. The secondary structures of the peptides in 85% trifluoroethanol (pH 6.0) were analyzed using an AVIV circular dichroism spectrometer at 25°C. Spectra were measured from 195 to 260 nm at 1-nm intervals, and mean residue molar ellipticity (MRE) was used to compare different peptides. Figure 1 shows an ␣-helical conformation characterized by a strong positive band at 195 nm and two negative bands at 208 and approximately 222 nm (12). The ␣-helical content of P-113 was estimated to be 2.9% using the ␤-structure selection (BeStSel) method (13). However, the ␣-helical contents of P-113Du and P-113Tri were 10.6% and 21.4%, respectively, suggesting the presence of a significant fraction of ␣-helix conformation.To examine the salt sensitivity of the peptides, spot assays were performed ( Fig. 2A). Cells (4.0 ϫ 10 5 cells) of the C. albicans strain SC5314 were incubated with different concentrations of sodium acetate (NaOAc) and peptides for 1 h. The mixtures were then spotted onto 1% yeast extract-2% peptone-2% glucose (YPD) agar. After 24 h of incubation, P-113 exhibited candidacidal activity in the presence of 12.5 mM sodium acetate but reduced activity in the presence of 62.25 and 93.75 mM salt. However, P-113Du and P-113Tri exhibited potent candidacidal activity even in the presence of 93.75 mM sodium acetate ( Fig. 2A). In addition, a previous study indicated that P-113 loses its bactericidal activity at pH 4.5 (14). Therefore, the pH sensitivities of the peptides were examined. P-113 exhibited candidacidal activity at pH 6 and 8, and...

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“…To overcome this drawback, we developed a strategy to increase the salt resistance of Trp-and His-rich AMPs by replacing their tryptophans or histidines with nonnatural bulky amino acid ␤-naphthylalanine (30). After which, we modified this strategy by adding ␤-naphthylalanine to termini of the short antimicrobial peptide S1 (Ac-KKWRKWLAKK-NH 2 ) to boost its salt resistance and serum proteolytic stability (31).…”

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Ultrashort Antimicrobial Peptides with Antiendotoxin Properties

Chih

Lin

Yip

et al. 2015

Antimicrob Agents Chemother

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bRelease of lipopolysaccharide (LPS) (endotoxin) from bacteria into the bloodstream may cause serious unwanted stimulation of the host immune system. Some but not all antimicrobial peptides can neutralize LPS-stimulated proinflammatory responses. Salt resistance and serum stability of short antimicrobial peptides can be boosted by adding ␤-naphthylalanine to their termini. Herein, significant antiendotoxin effects were observed in vitro and in vivo with the ␤-naphthylalanine end-tagged variants of the short antimicrobial peptides S1 and KWWK.

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Easy Strategy To Increase Salt Resistance of Antimicrobial Peptides

Cited by 105 publications

References 22 publications

Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states

Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states

The Antimicrobial Peptides P-113Du and P-113Tri Function against Candida albicans

Ultrashort Antimicrobial Peptides with Antiendotoxin Properties

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