Heterologous expression of a broad-spectrum chimeric antimicrobial peptide in Lactococcus lactis: Its safety and molecular modeling evaluation

Tanhaieian, Abass; Sekhavati, Mohammad Hadi; Ahmadi, Farajollah Shahriari; Mamarabadi, Mojtaba

doi:10.1016/j.micpath.2018.09.016

Cited by 24 publications

(20 citation statements)

References 45 publications

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“…Chemical modifications and non peptide mimetics design can improve the stability (Helmer and Schmitz, 2016;Gurwitz, 2017), while heterologous expression is a promising way to produce the peptides for large scale application. Though there exist some obstacles in this technique, such as toxicity and low expression, in recent years many methods have been developed to solve these problems, for example, expression of a chimeric peptide, upstream insertion of Asp-Pro sequence to membrane peptide to overcome its toxicity, and secretory expression (Montigny et al, 2004;Tanhaieian et al, 2018;Tanhaeian et al, 2018). As for how to use the peptide identified in this work to fight WSSV, in the following study we will manage to build a cyanobacterial expression system to produce the peptide, which can be applied easily by feeding the shrimp with the genetically modified blue alga.…”

Section: Discussionmentioning

confidence: 99%

Computational identification of self-inhibitory peptides from white spot syndrome virus envelope protein VP28

Qiu

et al. 2019

Aquaculture Reports

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Since effective chemotherapeutics or preventive measures are still unavailable, finding feasible approaches against white spot syndrome virus (WSSV) has always been the vital subject in shrimp farming field. Envelope proteins are the ideal targets for antiviral strategies development due to their indispensable roles in virus entry, and inhibitory peptides targeting them have been proved to be promising in blocking virus infection. In this study, the Wimley-White interfacial hydrophobicity scale (WWIHS) in combination with known structural data was applied to identify potential inhibitory peptides that targeted the envelope protein VP28 of WSSV. Results showed that two potential inhibitory peptides were identified, one of which exhibited not only obvious antiviral activity, but also broad-spectrum antimicrobial activity. The inhibitory peptide identified here can serve as a lead compound for anti-WSSV strategies development.

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Section: Discussionmentioning

confidence: 99%

Computational identification of self-inhibitory peptides from white spot syndrome virus envelope protein VP28

Qiu

et al. 2019

Aquaculture Reports

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“…While the use of antibiotics has been banned in many parts of the world, such European Union, due to health concerns related to emerging antibiotic-resistance pathogens and also drug residues in poultry products, researchers have investigated for alternative additives to restrain NE. Recently, more attentions have inclined to AMPs due to their beneficial roles on health attributes and to prophylactic effects against pathogenic invasion [12, 13 and 17]. Therefore, the principal objective of the current study was to investigate the effects of antimicrobial peptide, cLFchimera, on various productive and health parameters in chickens experimentally challenged with NE.…”

Section: Discussionmentioning

confidence: 99%

“…The AMP used in the present study was derived from camel lactoferrin (cLF) consisting of 42 amino acids, which were recently generated in our lab recently (for more details regarding the peptide cLF chimera production, please review previous papers [12, 13 and 14]. Briefly, preparation of recombinant plasmid vector was conducted through transforming recombinant expression vector harboring synthetic cLFchimera into DH5α bacterium [12, 13 and 14]. Next, the latter bacterial colonies were cultured to harvest plasmid extraction.…”

Section: Methodsmentioning

confidence: 99%

“…cLFchimera is a heterodimeric peptide designed to mimic two antimicrobial domains, Lactoferricin (LFcin) and Lactoferrampin (LFampin), which are present in the N1-domain of camel lactoferrin (cLF) [12]. More recently, the recombinant form of cLFchimera has been cloned and expressed in E. coli [12] and L. lactic [13] in our lab. The results of in vitro studies showed that cLF36 has antibacterial [12, 13 and 14] antiviral [15], and anticancer [16] properties.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, the recombinant form of cLFchimera has been cloned and expressed in E. coli [12] and L. lactic [13] in our lab. The results of in vitro studies showed that cLF36 has antibacterial [12, 13 and 14] antiviral [15], and anticancer [16] properties. Furthermore, the results of an in vivo experiment showed that supplementing E. coli challenged broilers with cLFchimera improved villi morphology in the jejunum, restored microbial balance in the ileum, and improved gene expression of cytokines and tight junctions in the jejunum of challenged broiler chickens [17].…”

Section: Introductionmentioning

confidence: 99%

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Effects of cLFchimera, a recombinant antimicrobial peptide, on intestinal morphology, microbiota, and gene expression of immune cells and tight junctions in broiler chickens challenged withC. perfringens

Daneshmand

Kermanshahi

et al. 2019

Preprint

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24The current study was conducted to investigate the effects of cLFchimera, a recombinant 25 antimicrobial peptide (AMP), on various productive performance and gut health attributes of 26 broilers experimentally challenged with Clostridium perfringens (Cp). Three hundred and sixty 1-27 day-old chickens were randomly allocated to 4 treatments of 6 replicates as follows: T1) 28 unchallenged group fed with corn-soybean meal (CSM) without Cp challenge and additives; T2) 29 challenge group fed with CSM and challenged with Cp without any additives; T3) peptide group 30 challenged with NE supplemented with 20 mg cLF36/kg diet (AMP); T4) antibiotic group 31 challenged with NE and supplemented with 45 mg antibiotic (bacitracin methylene disalicylate)/kg 32 diet (antibiotic). Birds had free access to feed and water, sampling for villi morphology and ileal 33 microbiota were performed on days 10 and 22, while jejunal section was sampled for gene 34 expression of cytokines, tight junctions proteins, and mucin only on day 22. Results showed that 35 AMP ameliorated NE-related lesion in the jejunum and ileum and reduced mortality in challenged 36 birds compared to challenge group with Cp without any additives. Also, supplementing challenged 37 birds with AMP improved growth performance and reconstructed villi morphology. While 38 antibiotic non-selectively reduced the count of bacteria, AMP positively restored ileal microflora 39 in favor of good bacteria (i.e. Bifidobacteria spp. and Lactobacillus spp.). AMP beneficially 40 regulated the expression of cytokines, junctional proteins, and mucin in the jejunum of challenged 41 birds with Cp. Since cLFchimera ameliorated NE lesion score, reduced mortality, improved 42 productive performance and gut health attributes in chickens compared to challenged group and 43 also were mostly similar with those of antibiotics and therefore, it could be concluded that this 44 chimeric peptide can be a worthy candidate to substitute growth promoter antibiotics, while more 45 research is required to unveil the exact mode of action of this synthetic peptide. 46 47 Author summary 48 Necrotic enteritis (NE) is a detrimental enteric disease in the poultry industry worldwide. The 49 etiological factor of this disease is Clostridium perfringens, which is gram-positive anaerobic 50 bacterium. This bacterium is common inhabitant of the intestine in lower counts (105), but it 51 becomes pathogenic in higher counts and can secrete NetB toxin, which is the main cause of 52 inducing NE in broilers. Due to the emergence of antibiotic-resistant bacteria, new generation of 53 antimicrobial additives such as antimicrobial peptides (AMPs) has been introduced to the poultry 54 industry. AMPs are small molecules with 12-50 amino acids having antibacterial activity. 55 Recently, we extracted new AMP from camel milk, expressed in E. coli, refined and lyophilized 56 to produce purified peptides. The current study investigated the effects of this peptide on 57 prevention of NE in broilers. Results showed th...

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N‐terminal acetylation of antimicrobial peptide L163 improves its stability against protease degradation

Yang

et al. 2021

Journal of Peptide Science

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Antimicrobial peptide L163 was computationally designed by our laboratory; L163 is active against multidrug‐resistant (MDR) bacteria but is easily degraded in the plasma and by trypsin. Amino acid substitution, cyclization, and amino‐terminal (N‐terminal) acetylation were performed to obtain L163 analogs with high stability in the plasma and in trypsin solutions. The stability, antimicrobial activity, and biosafety of L163 and its analogs were investigated. Comparison with unmodified L163 indicated that N‐terminal acetylation enhanced the stability against pH, plasma, and trypsin degradation, and phenylalanine (Phe) substitution for leucine (Leu) and cysteine bridge (S–S) cyclization decreased the stability. N‐terminal acetylation also enhanced antimicrobial activity against MDR Streptococcus Sc181, Listeria monocytogenes, and Enterococcus E1478F; did not change the activity against MDR Staphylococcus aureus 9, Staphylococcus sciuri P254, and Staphylococcus aureus RN4220; and decreased the activity against Candida tropicalis, Candida albicans, and Enterococcus faecalis Fbc35. Phe substitution for Leu and S–S cyclization decreased the antimicrobial activity. The negative effect of these modifications was detected against biofilm formation by the tested microbial strains. Comparison of Phe substitution for Leu and S–S cyclization indicated that N‐terminally acetylated L163 (L163‐Ac) is the best candidate. L163‐Ac peptide had the highest antibacterial activity and enhanced tolerance to temperature, pH, plasma, and trypsin and low toxicity.

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Heterologous expression of a broad-spectrum chimeric antimicrobial peptide in Lactococcus lactis: Its safety and molecular modeling evaluation

Cited by 24 publications

References 45 publications

Computational identification of self-inhibitory peptides from white spot syndrome virus envelope protein VP28

Computational identification of self-inhibitory peptides from white spot syndrome virus envelope protein VP28

Effects of cLFchimera, a recombinant antimicrobial peptide, on intestinal morphology, microbiota, and gene expression of immune cells and tight junctions in broiler chickens challenged withC. perfringens

N‐terminal acetylation of antimicrobial peptide L163 improves its stability against protease degradation

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