Boosting Salt Resistance of Short Antimicrobial Peptides

Chu, Hung-Lun; Yu, Huiyuan; Yip, Bak-Sau; Chih, Ya-Han; Liang, Chong-Wen; Cheng, Hsi-Tsung; Cheng, Jya‐Wei

doi:10.1128/aac.00252-13

Cited by 102 publications

(96 citation statements)

References 25 publications

(4 reference statements)

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“…Our data indicated that A-hBD-2 has stronger anti-S. aureus activity under various concentrations (50 μg/mL, 70 μg/mL, and 100 μg/mL) compared with hBD-2. Natural AMPs lose their antimicrobial activity at physiological salt concentrations, thereby limiting their potential clinical application [16]. Our study found that both hBD-2 and A-hBD-2 had lower antibacterial abilities with increased NaCl concentrations.…”

Section: Discussionmentioning

confidence: 74%

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

Mi¹,

Liu²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca²⁺ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

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Section: Discussionmentioning

confidence: 74%

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

Mi¹,

Liu²,

Liu³

et al. 2018

Cell Physiol Biochem

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“…Serum inactivates peptides either through cleavage by proteases or through binding with proteins or lipids (30) We observed that RRIKA but not RR retained its bactericidal activity, although at a lower rate, in the presence of 10% FBS. Furthermore, both RRIKA and RR retained their antibacterial activity when tested in increasing concentration of NaCl and MgCl 2 , in contrast to many well-studied AMPs (such as LL-37, human ␤-defensin-1, gramicidins, bactenecins, and magainins) which showed substantially reduced antibacterial activities under the same conditions (11). Previously, Turner et al reported that LL-37 and human neutrophil peptide-1 (HNP-1) demonstrated 12-fold and 100-fold increases in the MIC of MRSA, respectively, when 100 mM NaCl was added to the test medium (10).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, their production cost is high (8,9). In addition, many natural AMPs lose their antimicrobial activity in physiological salt concentrations (10,11). These characteristics have substantially hindered their pharmaceutical development as new therapeutic agents.…”

mentioning

confidence: 99%

Targeting Methicillin-Resistant Staphylococcus aureus with Short Salt-Resistant Synthetic Peptides

Mohamed

Hamed

Panitch

et al. 2014

Antimicrob Agents Chemother

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bThe seriousness of microbial resistance combined with the lack of new antimicrobials has increased interest in the development of antimicrobial peptides (AMPs) as novel therapeutics. In this study, we evaluated the antimicrobial activities of two short synthetic peptides, namely, RRIKA and RR. These peptides exhibited potent antimicrobial activity against Staphylococcus aureus, and their antimicrobial effects were significantly enhanced by addition of three amino acids in the C terminus, which consequently increased the amphipathicity, hydrophobicity, and net charge. Moreover, RRIKA and RR demonstrated a significant and rapid bactericidal effect against clinical and drug-resistant Staphylococcus isolates, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA), linezolid-resistant S. aureus, and methicillin-resistant Staphylococcus epidermidis. In contrast to many natural AMPs, RRIKA and RR retained their activity in the presence of physiological concentrations of NaCl and MgCl 2 . Both RRIKA and RR enhanced the killing of lysostaphin more than 1,000-fold and eradicated MRSA and VRSA isolates within 20 min. Furthermore, the peptides presented were superior in reducing adherent biofilms of S. aureus and S. epidermidis compared to results with conventional antibiotics. Our findings indicate that the staphylocidal effects of our peptides were through permeabilization of the bacterial membrane, leading to leakage of cytoplasmic contents and cell death. Furthermore, peptides were not toxic to HeLa cells at 4-to 8-fold their antimicrobial concentrations. The potent and salt-insensitive antimicrobial activities of these peptides present an attractive therapeutic candidate for treatment of multidrug-resistant S. aureus infections.

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“…After incubation at 37°C for 2, 4, 6, or 8 h, the remaining amount of peptides was determined by reverse-phase HPLC [34]. All stability tests in serum, saliva, BHI medium and PBS were repeated three times.…”

Section: Nal-p-113 Stability Testmentioning

confidence: 99%

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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Boosting Salt Resistance of Short Antimicrobial Peptides

Cited by 102 publications

References 25 publications

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

Targeting Methicillin-Resistant Staphylococcus aureus with Short Salt-Resistant Synthetic Peptides

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

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