|
|
|
| Research Progress in Biological Characterisation and Inhibitory Mechanism of Microcin J25 |
| LIU Yan1, GUO Gan-Tong1, HE Tao1, ZHANG Fan1, WANG Ya-Jie1, WU Jin-Mei2, QU Dong-Jing1,* |
1 Sinagri YingTai Bio-peptide Co., Ltd., Zhengzhou 450000, China; 2 College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China |
|
|
|
|
Abstract Microcin J25 (MccJ25) is a lasso-type antimicrobial peptide (AMP) derived from Escherichia coli, distinguished by its broad-spectrum antibacterial activity, low cytotoxicity, and negligible propensity to elicit bacterial drug resistance. Its unique lasso topology endows Mcc J25 with exceptional stability, rendering it highly resistant to harsh environmental conditions. Mcc J25 exerts bacteriostatic or bactericidal effects on target pathogens by inhibiting bacterial RNA polymerase activity and disrupting the membrane respiratory chain. Furthermore, this peptide mediates anti-inflammatory activity through the modulation of host immune responses and intestinal microecological homeostasis. Leveraging its pleiotropic anti-inflammatory mechanisms and synergistic antibacterial efficacy, Mcc J25 has emerged as a prime candidate for the development of next-generation antimicrobial agents. Herein, current research advances were synthesized to summarize the core biological properties and primary antibacterial pathways of Mcc J25, and its translational potential was further evaluated based on these characteristics, with the aim of providing a theoretical framework for future antimicrobial drug discovery and development.
|
|
Received: 01 September 2025
|
|
|
|
Corresponding Authors:
*znytlz@126.com
|
|
|
|
[1] Adelman K, Yuzenkova J, La Porta A, et al.2004. Molecular mechanism of transcription inhibition by peptide antibiotic microcin J25[J]. Molecular Cell, 14(6): 753-762. [2] Asensio C, Perez-Diaz J C.1976. A new family of low molecular weight antibiotics from enterobacteria[J]. Bioche-mical and Biophysical Research Communications, 69(1): 7-14. [3] Baquero F, Beis K, Craik D J, et al.2024. The pearl jubilee of microcin J25: Thirty years of research on an exceptional lasso peptide[J]. Natural Product Reports, 41(3): 469-511. [4] Bellomio A, Rintoul M R, Morero R D.2003. Chemical modification of microcin J25 with diethylpyrocar-bonate andcarbodiimide: Evidence for essential histidyl and carboxyl residues[J]. Biochemical and Biophysical Research Communications, 303(2): 458-462. [5] Bellomio A, Vincent P A, De Arcuri B F, et al.2007. Microcin J25 has dual and independent mechanisms of action in Escherichia coli:RNA polymerase inhibition and increased superoxide production[J]. Journal of Bacteriology, 189(11): 4180-4186. [6] Blond A, Péduzzi J, Goulard C, et al.1999. The cyclic structure of microcin J25, a 21-residue peptide antibiotic from Escherichia coli[J]. European Journal of Biochemistry, 259(3):7 47-755. [7] Borisov V B, Gennis R B, Hemp J, et al.2011. The cytochrome bd respiratory oxygen reductases[J]. Biochimica et Biophysica Acta, 1807(11): 1398-1413. [8] Borisov V B, Verkhovsky M I.2015. Oxygen as acceptor[J]. EcoSal Plus, 6(2): ESP-0012-2015. [9] Bountra K, Hagelueken G, Choudhury H G, et al.2017. Structural basis for antibacterial peptide selfimmunity by the bacterial abc transporter McjD[J]. The EMBO Journal, 36(20): 3062-3079. [10] Braffman N R,Piscotta F J,Hauver J,et al.2019. Structural mechanism of transcription inhibition by lasso peptides microcin J25 and capistruin[J]. Proceedings of the National Academy of Sciences of the USA, 116(4): 1273-1278. [11] Chalon M C, Bellomio A, Solbiati J O, et al.2009. Tyrosine 9 is the key amino acid in microcin J25 superoxide overproduction[J]. Fems Microbiology Letters, 300(1): 90-96. [12] Chalon M C, Wilke N, Pedersen J, et al.2011. Redoxactive tyrosine residue in the microcin J25 molecule[J]. Biochemical and Biophysical Research Communications, 406(3): 366-370. [13] Cid M C, Unizony S H, Blockmans D, et al.2022. Efficacy and safety of mavrilimumab in giant cell arteritis:A phase2, randomised, doubleblind, placebocontrolled trial[J]. Annals of the Rheumatic Diseases, 81(5): 653-661. [14] Delgado M A, Rintoul M R, Farias R N, et al.2001. Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25[J]. Journal of Bacteriology,183(15): 4543-4550. [15] Delgado M A,Vincent P A, Farias R N,et al.2005. Yoji of Escherichia coli functions as a microcin J25 efflux pump[J]. Journal of Bacteriology, 187(10): 3465-3470. [16] Destoumieux-Garzon D, Peduzzi J, Rebuffat S.2002. Focus on modified microcins: Structural features and mechanisms of action[J]. Biochimie, 84(5-6): 511-519. [17] Ding X, Yu H, Qiao S.2020. Lasso peptide microcin J25 effectively enhances gut barrier function and modulates inflammatory response in an enterotoxigenic Escherichia coli challenged mouse model[J]. International Journal of Molecular Sciences, 21(18): 6500. [18] Duquesne S, Destoumieux-Garzon D, Peduzzi J, et al.2007. Microcins, gene encoded antibacterial peptides from enterobacteria[J]. Natural Product Reports, 24(4): 708-734. [19] Elsherif W M, Hassanien A A, Zayed G M, et al.2024. Natural approach of using nisin and its nanoform as food biopreservatives against methicillin resistant staphylococcus aureus and E.coli O157: H7 in yoghurt[J]. Bmc Veterinary Research, 20(1): 192. [20] Ergün F C, Kars M D, Kars G.2025. Development and characterization of LL37 antimicrobial-peptide-loaded chitosan nanoparticles: An antimicrobial sustained release system[J]. Polymers (Basel). 17(13): 1884. [21] Ferguson A L, Zhang S, Dikiy I, et al.2010. An experimental and computational investigation of spontaneous lasso formation in microcin J25[J]. Biophysical Journal, 99(9): 3056-3065. [22] Flaherty R A, Freed S D, Lee S W.2014. The wide world of ribosomally encoded bacterial peptides[J]. PLOS Pathogens, 10(7): e1004221. [23] Galvan A E, Chalon M C, Schurig-Briccio L A, et al.2018. Cytochromes bdi and bo(3) are essential for the bactericidal effect of microcin J25 on Escherichia coli cells[J]. Biochim Biophys Acta Bioenerg, 1859(2): 110-118. [24] Hegemann J D, De Simone M, Zimmermann M, et al.2014. Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides[J]. Journal of Medicinal Chemistry, 57(13): 5829-5834. [25] Imlay J A.2013. The molecular mechanisms and physiological consequences of oxidative stress: Lessons from a model bacterium[J]. Nature Reviews Microbiology, 11(7): 443-454. [26] Jeanne D F K, Hegemann J D, Zirah S, et al.2019. Evidence of cis/transisomerization at Pro7/Pro16 in the lasso peptide microcin J25[J]. Journal of the American Society for Mass Spectrometry, 30(6): 1038-1045. [27] Ji Q, Zhou B, Shen T, et al.2023. The lasso structure, biosynthesis, bioactivities and potential applications of microcin J25: A novel antibacterial agent with unique mechanisms[J]. Engineering Microbiology, 3(3): 100096. [28] Jittawuttipoka T, Buranajitpakorn S, Vattanaviboon P, et al.2009. The catalase-peroxidase katg is requireed for virulence of Xanthomonas campestris pv. campestris in a host plant by providing protection against low levels of H2O2[J]. Journal of Bacteriology, 191(23): 7372-7377. [29] Kunakom S, Eustáquio A S.2020. Heterologous production of lasso peptide capistruin in a burkholderia host[J]. Acs Synthetic Biology, 9(2): 241-248. [30] Leibovic K N.2001. The response gradient along the rod outer segment: Cgmp, age and calcium[J]. Progress in Brain Research, 131: 359-368. [31] Li Z, Chinnasamy S, Zhang Y, et al.2021. Molecular dynamics simulation and binding free energy calculations of microcin J25 binding to the FhuA receptor[J]. Journal of Biomolecular Structure & Dynamics, 39(7): 2585-2594. [32] Malik I T, Hegemann J D, Brotz-Oesterhelt H.2021. Generation of lasso peptide-based clpp binders[J]. International Journal of Molecular Sciences, 23(1): 465. [33] Mathavan I, Beis K.2012. The role of bacterial membrane proteins in the internalization of microcin J25 and Mcc B17[J]. Biochemical Society Transactions, 40(6): 1539-1543. [34] May M.2014. Drug development: Time for teamwork[J]. Nature, 509(7498): S4-S5. [35] Messner K R, Imlay J A.1999. The identification of primary sites of superoxide and hydrogen peroxide formation in the aerobic respiratory chain and sulfite reductase complex of Escherichia coli[J]. Journal of Biological Chemistry, 274(15): 10119-10128. [36] Messner K R, Imlay J A.2002. Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase[J]. Journal of Biological Chemistry, 277(45): 42563-42571. [37] Mukhopadhyay J, Sineva E, Knight J, et al.2004. Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the rRNA polymerase secondary channel[J]. Molecular Cell, 14(6): 739-751. [38] Mwangi J, Yin Y, Wang G, et al.2019. The antimicrobial peptide ZY4 combats multidrug-resistant pseudomonas aeruginosa and acinetobacter baumannii infection[J]. Proceedings of the National Academy of Sciences of the USA, 116(52): 26516-26522. [39] Naimi S, Zirah S, Greppi A, et al.2022. Impact of microcin J25 on the porcine microbiome in a continuous culture model[J]. Frontiers in Microbiology, 13: 930392. [40] Naimi S, Zirah S, Hammami R, et al.2018. Fate and biological activity of the antimicrobial lasso peptide microcin J25 under gastrointestinal tract conditions[J]. Frontiers in Microbiology, 9: 1764. [41] Nawrocki E M, Mosso H M, Dudley E G.2020. A toxic environment: A growing understanding of how microbial communities affect Escherichia coli O157: H7 shiga toxin expression[J]. Applied and Environmental Microbiology, 86(24): e00509-20. [42] Novy T C T, Joni I M, Lesmana R,et al.2025. Chitosan nanoparticles as an alternative therapeutic approach for knee osteoarthritis treatment: A systematic review[J]. International Journal of Nanomedicine, 20: 6187-6203. [43] Ongpipattanakul C, Desormeaux E K, DiCaprio A, et al.2022. Mechanism of action of ribosomally synthesized and posttranslationally modified peptides[J]. Chemical Reviews, 122(18): 14722-14814. [44] Parker J K, Davies B W.2022. Microcins reveal natural mechanisms of bacterial manipulation to inform therapeutic development[J]. Microbiology (Reading), 168(4): 001175. [45] Pavlova O, Mukhopadhyay J, Sineva E, et al.2008. Systematic structure-activity analysis of microcin J25[J]. Journal of Biological Chemistry, 283(37): 25589-25595. [46] Pomares M F, Delgado M A, Corbalán N S, et al.2010. Sensitization of microcin J25 resistant strains by a membrane permeabilizing peptide[J]. Applied and Environmental Microbiology, 76(20): 6837-6842. [47] Rebuffat S.2012. Microcins in action: Amazing defence strategies of enterobacteria[J]. Biochemical Society Transactions, 40(6): 1456-1462. [48] Rebuffat S, Blond A, Destoumieux-Garzon D, et al.2004. Microcin J25, from the macrocyclic to the lasso structure:Implications for biosynthetic, evolutionary and biotechnological perspectives[J]. Current Protein & Peptide Science, 5(5): 383-391. [49] Rintoul M R, de Arcuri B F, Morero R D.2000. Effects of the antibiotic peptide microcin J25 on liposomes: Role of acyl chain length and negatively charged phospholipid[J]. Biochim Biophys Acta, 1509(1-2): 65-72. [50] Rintoul M R, de Arcuri B F, Salomon R A, et al.2001. The antibacterial action of microcin J25: Evidence for disruption of cytoplasmic membrane energization in Salmonella newport[J]. Fems Microbiology Letters, 204(2): 265-270. [51] Rintoul M R, Morero R D, Dupuy F G.2015. The antimicrobial peptide microcin J25 stabilizes the gel phase of bacterial model membranes[J]. Colloids and Surfaces. B, Biointerfaces, 129: 183-190. [52] Salomon R A, Farias R N.1992. Microcin 25, a novel antimicrobial peptide produced by Escherichia coli[J]. Journal of Bacteriology, 174(22): 7428-7435. [53] Semenova E, Yuzenkova Y, Peduzzi J, et al.2005. Structureactivity analysis of microcin J25: Distinct parts of the threaded lasso molecule are responsible for interaction with bacterial RNA polymerase[J]. Journal of Bacteriology, 187(11): 3859-3863. [54] Shang L, Yang F, Chen Q, et al.2024. Bacteriocin microcin J25's antibacterial infection effects and novel nonmicrobial regulatory mechanisms: Differential regulation of dopaminergic receptors[J]. Journal of Animal Science and Biotechnology, 15(1): 156. [55] Shang L, Yu H, Liu H, et al.2021. Recombinant antimicrobial peptide microcin J25 alleviates dssinduced colitis via regulating intestinal barrier function and modifying gut microbiota[J]. Biomedicine & Pharmacotherapy, 139: 111127. [56] Smits S H J, Schmitt L, Beis K.2020. Selfimmunity to antibacterial peptides by ABC transporters[J]. Febs Letters, 594(23): 3920-3942. [57] Solbiati J O, Ciaccio M, Farias R N, et al.1999. Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25[J]. Journal of Bacteriology, 181(8): 2659-2662. [58] Solbiati J O, De Cristóbal R E, Zenoff A M,et al.2006.Insights into the recognition of microcin J25 by the inner membrane receptor SbmA[J]. Journal of Bacteriology, 188(10): 3658-3665. [59] Soltani S, Hammami R, Cotter P D, et al.2021. Bacteriocins as a new generation of antimicrobials: Toxicity aspects and regulations[J]. Fems Microbiology Reviews, 45(1): fuaa039. [60] Soudy R, Etayash H, Bahadorani K, et al.2017. Breast cancer targeting peptide binds keratin1: A new molecular marker for targeted drug delivery to breast cancer[J]. Molecular Pharmaceutics, 14(3): 593-604. [61] Tan H, Liu W, Ho J, et al.2024. Structure prediction and protein engineering yield new insights into microcin J25 precursor recognition[J]. Acs Chemical Biology, 19(9): 1982-1990. [62] Telhig S, Ben Said L, Torres C, et al.2022. Evaluating the potential and synergetic effects of microcins against multidrugresistant enterobacteriaceae[J]. Microbiology Spectrum, 10(3): e0275221. [63] Telhig S, Pham N P, Ben Said L, et al.2024. Exploring the genetic basis of natural resistance to microcins[J]. Microbial Genomics, 10(2): 001156. [64] Varghese S, Tang Y, Imlay J A.2003. Contrasting sensitivities of Escherichia coli aconitases A and B to oxidation and iron depletion[J]. Journal of Bacteriology, 185(1): 221-230. [65] Vincent P A, Delgado M A, Farias R N, et al.2004. Inhibition of Salmonella enterica serovars by microcin J25[J]. Fems Microbiology Letters, 236(1): 103-107. [66] Wu Y, Zhu C, Chen Z, et al.2016. Protective effects of lactobacillus plantarum on epithelial barrier disruption caused by enterotoxigenic Escherichia coli in intestinal porcine epithelial cells[J]. Veterinary Immunology and Immunopathology, 172: 55-63. [67] Yan K P, Li Y, Zirah S, et al.2012. Dissecting the maturation steps of the lasso peptide microcin J25 in vitro[J]. Chembiochem, 13(7): 1046-1052. [68] Yang F, Yang F, Huang J, et al.2024. Microcin C7 as a potential antibacterial immunomodulatory agent in the postantibiotic era: Overview of its bioactivity aspects and applications[J]. International Journal of Molecular Sciences, 25(13): 7213. [69] Yang G, Shang L, Liu L, et al.2023. Engineering and purification of microcin C7 variants resistant to tyrpsin and analysis of their biological activity[J]. Antibiotics (Basel, Switzerland), 12(9): 1346. [70] Yu H, Ding X, Shang L, et al.2018. Protective ability of biogenic antimicrobial peptide microcin J25 against enterotoxigenic Escherichia coli induced intestinal epithelial dysfunction and inflammatory responses IPEC-J2 cells[J]. Frontiers in Cellular and Infection Microbiology, 8: 242. [71] Yu H, Li N, Zeng X, et al.2019. A comprehensive antimicrobial activity evaluation of the recombinant microcin J25 against the foodborne pathogens salmonella and E. coli O157: H7 by using a matrix of conditions[J]. Frontiers in Microbiology, 10: 1954. [72] Yu H, Shang L, Yang G, et al.2022. Biosynthetic microcin J25 exerts strong antibacterial, antiinflammatory activities, low cytotoxicity without increasing drug-resistance to bacteria target[J]. Frontiers in Immunology, 13: 811378. [73] Yu H T, Chen Y F, Sun M Cet al.2021. A novel polymeric nanohybrid antimicrobial engineered by antimicrobial peptide microcin J25 and chitosan nanoparticles exerts strong antibacterial and antiinflammatory activities[J]. Frontiers in Immunology, 12: 811381. [74] Yu H T, Ding X L, Li N, et al.2017. Dietary supplemented antimicrobial peptide microcin J25 improves the growth performance, apparent total tract digestibility, fecal microbiota, and intestinal barrier function of weaned pigs[J]. Journal of Animal Science, 95(11): 5064-5076. [75] Zhang G, Feng S, Qin M, et al.2024. Influence of PepF peptidase and sporulation on microcin J25 prodction in Bacillus subtilis[J]. Microbiology Spectrum, 12(7): e0374823. [76] Zhang G, Lin M, Qin M, et al.2023. Establishing heterologous production of microcins J25 and Y in Bacillus subtilis[J]. Journal of Agricultural and Food Chemistry, 71(14): 5600-5613. |
|
|
|