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Oral Administration of Antimicrobial Peptide NZ2114 Through the Microalgal Bait Tetraselmis subcordiformis (Wille) Butcher for Improving the Immunity and Gut Health in Turbot (Scophthalmus maximus L.)

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Abstract

Antibiotics are widely used in aquaculture to treat the bacterial diseases. However, the improper use of antibiotics could lead to environmental pollution and development of resistance. As a safe and eco-friendly alternative, antimicrobial peptides (AMPs) are commonly explored as therapeutic agents. In this study, a mutant strain of Tetraselmis subcordiformis containing AMP NZ2114 was developed and used as an oral drug delivery system to reduce the use of antibiotics in turbot (Scophthalmus maximus) aquaculture. The gut, kidney, and liver immune-related genes and their effects on gut digestion and bacterial communities in turbot fed with NZ2114 were evaluated in an 11-day feeding experiment. The results showed that compared with the group fed with wild-type T. subcordiformis, the group fed with T. subcordiformis transformants containing NZ2114 was revealed with decreased levels of both pro-inflammatory factors (TNF-α and IL-1β), inhibitory effect on Staphylococcus aureus, Vibrio parahaemolyticus, and Vibrio splendidus demonstrated by the in vitro simulation experiments, and increased richness and diversity of the gut microbiota of turbot. In conclusion, our study provided a novel, beneficial, and low-cost method for controlling bacteria in turbot culture through the oral drug delivery systems.

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Data Availability

The datasets presented in this study can be found in online repositories (https://www.ncbi.nlm.nih.gov/; with the accession PRJNA1015641).

References

  • Andes D, Craig W, Nielsen LA, Kristensen HH (2009) In vivo pharmacodynamic characterization of a novel plectasin antibiotic, NZ2114, in a murine infection model. Antimicrob Agents Chemother 53:3003–3009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Austin B, Morgan DA, Alderman DJ (1981) Comparison of antimicrobial agents for control of vibriosis in marine fish. Aquaculture 26:1–12

    Article  CAS  Google Scholar 

  • Barkia I, Saari N, Manning SR (2019) Microalgae for high-value products towards human health and nutrition. Mar Drugs 17(5)

  • Bolaños-Martínez OC, Mahendran G, Rosales-Mendoza S, Vimolmangkang S (2022) Current status and perspective on the use of viral-based vectors in eukaryotic microalgae. Mar Drugs 20(7)

  • Bondad-Reantaso MG, MacKinnon B, Karunasagar I, Fridman S, Alday-Sanz V, Brun E, Groumellec M, Li A, Surachetpong W, Karunasagar I, Hao B, Caputo A (2023) Review of alternatives to antibiotic use in aquaculture. Rev Aquac. 

    Article  Google Scholar 

  • Browne K, Chakraborty S, Chen R, Willcox MD, Black DS, Walsh WR, Kumar N (2020) A new era of antibiotics: the clinical potential of antimicrobial peptides. Int J Mol Sci 21(19)

  • Burel C, Boujard T, Kaushik SJ, Boeuf G, Van Der Geyten S, Mol KA, Kühn ER, Quinsac A, Krouti M, Ribaillier D (2000) Potential of plant-protein sources as fish meal substitutes in diets for turbot (Psetta maxima): growth, nutrient utilisation and thyroid status. Aquaculture 188:363–382

    Article  CAS  Google Scholar 

  • Chen H, Mao R, Teng D, Wang X, Hao Y, Feng X, Wang J (2017) Design and pharmacodynamics of recombinant NZ2114 histidine mutants with improved activity against methicillin-resistant Staphylococcus aureus. AMB Express 7:46

    Article  PubMed  PubMed Central  Google Scholar 

  • Dehghani J, Movafeghi A, Mathieu-Rivet E, Mati-Baouche N, Calbo S, Lerouge P, Bardor M (2022) Microalgae as an efficient vehicle for the production and targeted delivery of therapeutic glycoproteins against SARS-CoV-2 variants. Mar Drugs 20(11)

  • Fan W, Tang T, Qian Z, Wan H, Zhao S, Agyare OK, Jiang Z, Qu S (2020) The role of IL-1β in aortic aneurysm. Clin Chim Acta 504:7–14

    Article  CAS  Google Scholar 

  • Garcia-Beltran JM, Arizcun M, Chaves-Pozo E (2023) Antimicrobial peptides from photosynthetic marine organisms with potential application in aquaculture. Mar Drugs 21(5)

  • Goh WJ, Zou S, Ong WY, Torta F, Alexandra AF, Schiffelers RM, Storm G, Wang J, Czarny B, Pastorin G (2017) Bioinspired cell-derived nanovesicles versus exosomes as drug delivery systems: a cost-effective alternative. Sci Rep 7(1)

  • Gou X, Zhang L, Zhao S, Ma W, Yang Z (2021) Application of the combination of soybean lecithin and whey protein concentrate 80 to improve the bile salt and acid tolerance of probiotics. J Microbiol Biotechnol 31:840–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu M, Pan S, Li Q, Qi Z, Deng W, Bai N (2021a) Chitosan and chitooligosaccharides attenuate soyabean meal-induced intestinal inflammation of turbot (Scophthalmus maximus): possible involvement of NF-small ka, CyrillicB, activator protein-1 and mitogen-activated protein kinases pathways. Br J Nutr 126:1651–1662

    Article  CAS  PubMed  Google Scholar 

  • Gu QQ, Wang GH, Li NQ, Hao DF, Liu HM, Wang CB, Hu YH, Zhang M (2021b) Evaluation of the efficacy of a novel Vibrio vulnificus vaccine based on antibacterial peptide inactivation in turbot, Scophthalmus maximus. Fish Shellfish Immunol 118:197–204

    Article  CAS  PubMed  Google Scholar 

  • Guerreiro I, Enes P, Rodiles A, Merrifield D, Oliva-Teles A (2016) Effects of rearing temperature and dietary short-chain fructooligosaccharides supplementation on allochthonous gut microbiota, digestive enzymes activities and intestine health of turbot (Scophthalmus maximus L.) juveniles. Aquac Nutr 22:631–642

    Article  CAS  Google Scholar 

  • Guo G, Li K, Zhu Q, Zhao C, Li C, He Z, Hu S, Ren Y (2022) Improvements of immune genes and intestinal microbiota composition of turbot (Scophthalmus maximus) with dietary oregano oil and probiotics. Aquaculture 547.

  • Holland MC, Lambris JD (2002) The complement system in teleosts. Fish Shellfish Immunol 12:399–420

    Article  CAS  PubMed  Google Scholar 

  • Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI (2001) Molecular analysis of commensal host-microbial relationships in the intestine. Science 291:881–884

    Article  CAS  PubMed  Google Scholar 

  • Jia R, Cao L-P, Du J-L, He Q, Gu Z-Y, Jeney G, Xu P, Yin G-J (2020) Effects of high-fat diet on antioxidative status, apoptosis and inflammation in liver of tilapia (Oreochromis niloticus) via Nrf2, TLRs and JNK pathways. Fish Shellfish Immunol 104:391–401

    Article  CAS  PubMed  Google Scholar 

  • Kang SJ, Nam SH, Lee BJ (2022) Engineering approaches for the development of antimicrobial peptide-based antibiotics. Antibiotics (Basel) 11(10)

  • Kordon AO, Scott MA, Ibrahim I, Abdelhamed H, Ahmed H, Baumgartner W, Karsi A, Pinchuk LM (2016) Identification of Langerhans-like cells in the immunocompetent tissues of channel catfish, Ictalurus punctatus. Fish Shellfish Immunol 58:253–258

    Article  CAS  PubMed  Google Scholar 

  • Li C, Tian Y, Wang L, Zhang B, Ma Q, Hern ndez AnJ (2022a) Effects of replacing fishmeal by raw or Lactobacillus acidophilus-fermented soybean meal on growth, intestinal digestive and immune-related enzyme activities, morphology, and microbiota in turbot (Scophthalmus maximus L.). Aquac Nutr 2022:1–13

    Article  Google Scholar 

  • Li S, Luo X, Liao Z, Liang M, Xu H, Mai K, Zhang Y (2022b) Effects of lysophosphatidylcholine on intestinal health of turbot fed high-lipid diets. Nutrients 14(20)

  • Liu Y, Shi J, Tong Z, Jia Y, Yang B, Wang Z (2021) The revitalization of antimicrobial peptides in the resistance era. Pharmacol Res 163:105276

    Article  CAS  PubMed  Google Scholar 

  • Lou J, Duan H, Qin Q, Teng Z, Gan F, Zhou X, Zhou X (2023) Advances in oral drug delivery systems: challenges and opportunities. Pharmaceutics 15(2)

  • Ma K, Bao Q, Wu Y, Chen S, Zhao S, Wu H, Fan J (2020) Evaluation of microalgae as immunostimulants and recombinant vaccines for diseases prevention and control in aquaculture. Front Bioeng Biotechnol 8

  • Mamat NZ, Alfaro AC (2014) Evaluation of microalgal and formulated diets for the culture of the New Zealand pipi clam Paphiesaustralis. Int Aquat Res 6(1)

  • Naiel MAE, Ghazanfar S, Negm SS, Shukry M, Abdel-Latif HMR (2023) Applications of antimicrobial peptides (AMPs) as an alternative to antibiotic use in aquaculture – a mini-review. Ann Anim Sci 23:691–701

    Article  CAS  Google Scholar 

  • Pardo BG, Millan A, Gomez-Tato A, Fernandez C, Bouza C, Alvarez-Dios JA, Cabaleiro S, Lamas J, Lemos M, Martinez P (2012) Gene expression profiles of spleen, liver, and head kidney in turbot (Scophthalmus maximus) along the infection process with Philasterides dicentrarchi using an immune-enriched oligo-microarray. Mar Biotechnol (NY) 14:570–582

    Article  CAS  PubMed  Google Scholar 

  • Ramos-Vega A, Angulo C, Bañuelos-Hernández B, Monreal-Escalante E (2021) Microalgae-made vaccines against infectious diseases. Algal Res 58

  • Rima M, Fajloun Z, Sabatier JM, Bechinger B, Naas T (2021) Antimicrobial peptides: a potent alternative to antibiotics. Antibiotics (Basel) 10(9)

  • Saraiva A, Costa J, Eiras JC, Cruz C (2016) Histological study as indicator of juveniles farmed turbot. Scophthalmus Maximus l Health Status Aquaculture 459:210–215

    Google Scholar 

  • Scott GI, Porter DE, Norman RS, Scott CH, Uyaguari-Diaz MI, Maruya KA, Weisberg SB, Fulton MH, Wirth E, Moore J, Pennington PL, Schlenk D, Cobb GP, Denslow ND (2016) Antibiotics as CECs: an overview of the hazards posed by antibiotics and antibiotic resistance. Front Mar Sci 3

  • Shi Y, Zhong L, Zhong H, Zhang J, Che C, Fu G, Hu Y, Mai K (2022) Taurine supplements in high-fat diets improve survival of juvenile Monopterus albus by reducing lipid deposition and intestinal damage. Aquaculture 547

  • Shirouchi B, Kawahara Y, Kutsuna Y, Higuchi M, Okumura M, Mitsuta S, Nagao N, Tanaka K (2023) Oral administration of Chaetoceros gracilis—a marine microalga—alleviates hepatic lipid accumulation in rats fed a high-sucrose and cholesterol-containing diet. Metabolites 13(3)

  • Su J, Ye M, Lou Y, Yang Z, Sun T, Zhang R, Xu J, Zhou C, Yan X (2017) Low-molecular-mass organic acid and lipid responses of Isochrysis galbana Parke to high temperature stress during the entire growth stage. Algal Res 26:93–103

    Article  Google Scholar 

  • Su Y-L, Chen G, Chen L-S, Li J-Z, Wang G, He J-Y, Zhan TY, Li YW, Yan MT, Huang YH, Qin QW, Dan XM, Sun H-Y (2019) Effects of antimicrobial peptides on serum biochemical parameters, antioxidant activity and non-specific immune responses in Epinephelus coioides. Fish Shellfish Immunol 86:1081–1087

    Article  CAS  PubMed  Google Scholar 

  • Vanzolini T, Bruschi M, Rinaldi AC, Magnani M, Fraternale A (2022) Multitalented synthetic antimicrobial peptides and their antibacterial, antifungal and antiviral mechanisms. Int J Mol Sci 23(1)

  • Visan AI, Cristescu R (2023) Polysaccharide-based coatings as drug delivery systems. Pharmaceutics 15(9)

  • Wang K, Chu J, Hu Z, Qin S, Cui Y (2023a) Using bait microalga as an oral delivery vehicle of antimicrobial peptide for controlling Vibrio infection in mussels. Fish Shellfish Immunol 136:108713

    Article  CAS  PubMed  Google Scholar 

  • Wang K, Jiao X, Chu J, Liu P, Han S, Hu Z, Qin S, Cui Y (2023b) Bait microalga harboring antimicrobial peptide for controlling Vibrio infection in Argopecten irradians aquaculture. Aquaculture 565

  • Wang X, Teng D, Mao R, Hao Y, Yang N, Li Z, Wang J (2018) Increased intracellular activity of MP1102 and NZ2114 against Staphylococcus aureus in vitro and in vivo. Sci Rep 8(1)

  • Willms RJ, Jones LO, Hocking JC, Foley E (2022) A cell atlas of microbe-responsive processes in the zebrafish intestine. Cell Rep 38(5)

  • Yang P, Hu H, Li Y, Ai Q, Zhang W, Zhang Y, Mai K (2019) Effect of dietary xylan on immune response, tight junction protein expression and bacterial community in the intestine of juvenile turbot (Scophthalmus maximus L.). Aquaculture 512

  • Yu J, Wang X, Qian S, Liu P, Li X, Li J (2022) Exposure to nitrate induces alterations in blood parameter responses, liver immunity, and lipid metabolism in juvenile turbot (Scophthalmus maximus). Aquat Toxicol 251:106280

    Article  CAS  PubMed  Google Scholar 

  • Zhang D, Zhong D, Ouyang J, He J, Qi Y, Chen W, Zhang X, Tao W, Zhou M (2022) Microalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy. Nat Commun 13(1)

  • Zhao M, Liu L, Liu F, Liu L, Liu Z, Gao Y, Cao J (2023) Traditional Chinese medicine improves myasthenia gravis by regulating the symbiotic homeostasis of the intestinal microbiota and host. Front Microbiol 13

  • Zorinc ML, Demir-Yilmaz I, Formosa-Dague C, Vrana I, Gašparović B, Horvat L, Butorac A, Frkanec R, DeNardis NI (2023) Reconstructed membrane vesicles from the microalga Dunaliella as a potential drug delivery system. Bioelectrochemistry 150

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Acknowledgements

We are grateful to Prof. Zhangli Hu at Shenzhen University for technical assistance of NZ2114.

Funding

This study was supported by the National Natural Science Foundation of China (42176140, 31972815, 42307179, and 42176124), the Natural Science Foundation of Shandong Province (ZR2023ZD30, ZR2019ZD17, ZR2021MC051, and ZR2021QD137), the Scientific research fund of Binzhou Medical University (BY2021KYQD18, BY2021KYQD25, BY2021KYQD28, and BY2022KYQD01), and the Yantai Economic-Technological Development Area Innovation Pilot Project (2021RC007).

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Ting Yao: software, validation, formal analysis, data curation, and writing—original draft; Fengjie Sun: data curation and writing—review and editing; Zhengquan Gao: project administration, funding acquisition, and supervision; Bingkui Zhu: formal analysis and data curation; Subing Han: investigation and methodology; Hao Zhang: resources, formal analysis, and funding acquisition; Yuyang Ma: methodology and supervision; Yuyong Wu: validation and supervision; Chunxiao Meng: funding acquisition and supervision; Yulin Cui: funding acquisition, conceptualization, resources, methodology, writing—review and editing, and supervision.

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Correspondence to Zhengquan Gao or Yulin Cui.

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Yao, T., Sun, F., Zhu, B. et al. Oral Administration of Antimicrobial Peptide NZ2114 Through the Microalgal Bait Tetraselmis subcordiformis (Wille) Butcher for Improving the Immunity and Gut Health in Turbot (Scophthalmus maximus L.). Mar Biotechnol 26, 230–242 (2024). https://doi.org/10.1007/s10126-024-10289-w

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