Enhancing antimicrobial activity of mastoparan-B by amino acid substitutions

Yang, Mars J.; Lin, Wen-Yuh; Lin, Chun-Ching; Shyu, Ching-Lin; Hou, Roger F.; Tu, Wu‐Chun

doi:10.1016/j.aspen.2013.05.002

Cited by 6 publications

(5 citation statements)

References 55 publications

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“…Diverse mastoparan-like peptides have been reported to have antimicrobial activity, mostly acting against bacteria. , The variants R1 and R4 described here were mostly active against E. coli, P.…”

Section: Discussionmentioning

confidence: 80%

“…39 Diverse mastoparan-like peptides have been reported to have antimicrobial activity, mostly acting against bacteria. 37,40 The variants R1 and R4 described here were mostly active against E. coli, P. aeruginosa and S. aureus planktonic strains (Table 2). Similar findings were also reported by Lin et al, 41 who developed six mastoparan-like peptides that potentially inhibited E. coli and S. aureus.…”

Section: ■ Structural Analysismentioning

confidence: 97%

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Computer-Aided Design of Mastoparan-like Peptides Enables the Generation of Nontoxic Variants with Extended Antibacterial Properties

et al. 2019

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Diverse peptides have been evaluated for their activity against pathogenic microorganisms. Here, five mastoparan variants were designed based on mastoparan-L, among which two (R1 and R4) were selected for in-depth analysis. Mastoparan-L (parent/control), R1, and R4 inhibited susceptible/resistant bacteria at concentrations ranging from 2 to 32 μM, whereas only R1 and R4 eradicated Pseudomonas aeruginosa biofilms at 16 μM. Moreover, the toxic effects of mastoparan-L toward mammalian cells were drastically reduced in both variants. In skin infections, R1 at 64 μM was the most effective variant, reducing P. aeruginosa bacterial counts 1000 times on day 4 post-infection. Structurally, all of the peptides showed varying levels of helicity and structural stability in aqueous and membrane-like conditions, which may affect the different bioactivities observed here. By computationally modifying the physicochemical properties of R1 and R4, we reduced the cytotoxicity and optimized the therapeutic potential of these mastoparan-like peptides both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 80%

Section: ■ Structural Analysismentioning

confidence: 97%

Computer-Aided Design of Mastoparan-like Peptides Enables the Generation of Nontoxic Variants with Extended Antibacterial Properties

et al. 2019

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“…Investigations suggested two E. coli strains, S. xylosus and Citrobacter koseri at low dosages (0.1 mg/L), were sensitive to this compound (15). In another study, MP-B and its analogs were found to be safe to the probiotics after undergoing appropriate amino acid substitutions (16).…”

Section: Introductionmentioning

confidence: 97%

Evaluation Synergistic Effect of TiO2, ZnO Nanoparticles and Amphiphilic Peptides (Mastoparan-B, Indolicidin) Against Drug-Resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii

Masoumi

Shakibaie

Gholamrezazadeh

et al. 2018

Arch Pediatr Infect Dis

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Backgound: The aims of this study were to evaluate the antimicrobial properties and synergistic effects of nano-titanium dioxide (TiO2), nano-zinc oxide (ZnO) and two synthetic peptides (mastoparan-B, indolicidin) against drug-resistant strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Methods: From March to August 2015, a total of 30 (10 each) isolates of the above bacteria were recovered from patients in the ICU of two referral hospitals in Kerman, Iran. The sizes and purities of nano-TiO2, nano-ZnO were determined by scanning electron microscope (SEM) and X-ray diffraction (XRD). Similarly, mass spectroscopy and HPLC were used for checking the genunity of the peptides. Antibiotic sensitivity was determined by agar disk diffusion assay. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) activities of nanometals and synthetic peptides were assessed by CLSI broth microdilution test. Similarly, checkerboard and time-kill curve analysis were performed to determine the synergistic activities of these compounds. Results: Mastoparan-B had potent toxicity to all isolates with an average MIC 4 ± 0.2 mg/L, while TiO2-NP had lowest antimicrobial activity with MIC range 1280 ≥ ± 0.2 mg/L (P. aeruginosa growth was not inhibited by TiO2 and ZnO NPs). The bactericidal activity against the isolates in descending order was mastoparan-B, indolicidin, nano ZnO, and nano TiO2, respectively. Further investigation on synergism using fractional inhibitory concentration index (FIC) revealed that, nano-TiO2 and nano-ZnO combination had an additive effect (FIC = 0.95 ± 0.1) on A. baumannii and K. pneumoniae strains, whereas, P. aeruginosa isolates were indifferent to this combination (FIC ≥ 2 ± 0.2). In contrast, mastoparan-B and indolicidin combination displayed broad synergistic effect (FIC = 0.5 ± 0.1) on all the isolates and caused rapid killing of the organisms within 4 h of incubation. Conclusions: Our results showed that the combination of mastoparan-B and indolicidin peptides is a suitable candidate for substitution of the antibiotics for topical treatment of infections caused by drug-resistant bacteria.

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“…A common biological activity of MP peptides is the ability to promote cell lysis or, more specifically, haemolysis [41,42,[50][51][52][53]. This disruption of biological membranes by cationic peptides has been widely proposed as a general mechanism of antibiotic activity.…”

Section: Discussionmentioning

confidence: 99%

“…The privileged structure of MP and related sequences is readily modified either during or post synthesis and single amino acid substitutions within a tetradecapeptide helix can produce dramatic changes in biological activities [52][53][54] and/or membrane selectivity (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

The cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14

Howl

Jones

2018

Peptides

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Mastoparan (MP) peptides, distributed in insect venoms, induce a local inflammatory response post envenomation. Most endogenous MPs share common structural elements within a tetradecapeptide sequence that adopts an amphipathic helix whilst traversing biological membranes and when bound to an intracellular protein target. Rational modifications to increase cationic charge density and amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide and potent secretagogue. Following intracellular translocation, MitP is accreted by mitochondria thus indicating additional utility as an antimicrobial agent. Hence, the objectives of this study were to compare the antimicrobial activities of a structurally diverse set of cationic cell penetrating peptides, including both MP and MitP sequences, and to chemically engineer analogues of MitP for potential therapeutic applications. Herein, we confirm that, like MP, MitP is a privileged structure for the development of antimicrobial peptides active against both prokaryotic and eukaryotic pathogens. Collectively, MitP and target-selective chimeric analogues are broad spectrum antibiotics, with the Gram-negative A. baumannii demonstrating particular susceptibility. Modifications of MitP by amino acid substitution at position-14 produced peptides, Δ14MitP analogues, with unique pharmacodynamic properties. One example, [Ser]MitP, lacks both cytotoxicity against human cell lines and mast cell secretory activity yet retains selective activity against the encapsulated yeast C. neoformans.

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Enhancing antimicrobial activity of mastoparan-B by amino acid substitutions

Cited by 6 publications

References 55 publications

Computer-Aided Design of Mastoparan-like Peptides Enables the Generation of Nontoxic Variants with Extended Antibacterial Properties

Computer-Aided Design of Mastoparan-like Peptides Enables the Generation of Nontoxic Variants with Extended Antibacterial Properties

Evaluation Synergistic Effect of TiO2, ZnO Nanoparticles and Amphiphilic Peptides (Mastoparan-B, Indolicidin) Against Drug-Resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii

The cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14

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