设为首页 |  加入收藏
首页首页 期刊简介 消息通知 编委会 电子期刊 投稿须知 广告合作 联系我们
抗菌肽在骨感染治疗中的研究进展

Research progress of antimicrobial peptides in the treatment of bone infection

作者: 王淦张妍崔宇韬刘贺田宇航李少荣范谊吴丹凯彭传刚  
单位:吉林大学第二医院&nbsp;(长春130041) <p>通信作者:彭传刚。E-mail: pengcg@jlu.edu.cn</p> <p>&nbsp;</p>
关键词: 抗菌肽;骨感染;抗菌机制;药物载体;治疗应用  
分类号:R318 <p>&nbsp;</p>
出版年·卷·期(页码):2022·41·2(208-214)
摘要:

创伤后骨髓炎是骨组织感染的严重并发症,使患者长期卧床,生活质量下降,最终残疾甚至危及生命。目前临床控制骨感染的首选疗法是彻底清创外加全身和局部使用抗生素。但细菌在局部感染部位的繁殖可形成生物膜,从而使细菌难以被清除,成为控制感染的难点。此外,长期使用抗生素还会引起各种全身不良反应并增加细菌耐药性。抗菌肽(antimicrobial peptides, AMPs)是种类丰富的新兴抗菌物质,能通过破坏细菌细胞膜或细胞壁的抗菌机制对抗耐药菌,引起研究者的青睐。考虑到抗菌肽局部给药疗效更好,近年来研究者对AMPs与局部药物递送相结合治疗骨感染进行了研究。如骨水泥、钛合金假体、水凝胶以及发展较快的纳米粒子可将抗菌肽稳定释放而不影响抗菌肽的生物活性。根据AMPs的特点、结构分类及抗菌机制选取合适的药物载体搭载AMPs或与抗生素共同整合从而制作出具有较强抗菌功能的材料是治疗骨组织感染的一种有效且有前景的方法。本文介绍了AMPs的抗菌机制及将其运送至局部靶向部位的一些载体,总结讨论AMPs对抗耐药病原体的优势,并分析了AMPs在现有的研究环境下所要处理的优先事项和应用前瞻。

 

Post-traumatic osteomyelitis is a serious complication of bone tissue infection, which leads to long-term bedridden patients, decreased quality of life, and eventually disability or even life-threatening. At present, the preferred treatment for clinical control of bone infection is complete debridement plus systemic and local antibiotic use. However, the reproduction of bacteria in the locally infected parts can form biofilms, which makes it difficult to remove the bacteria and becomes the difficulty in infection control. In addition, long-term use of antibiotics can cause a variety of systemic adverse reactions and increase bacterial resistance. Antimicrobial peptides are a variety of emerging antimicrobial substances, which can fight against drug-resistant bacteria by destroying the antimicrobial mechanism of bacterial cell membrane or cell wall. Considering that local administration of antimicrobial peptides has better efficacy, researchers have studied the combination of antimicrobial peptides and local drug delivery in the treatment of bone infection in recent years.  Such as bone cement, titanium alloy prostheses ,hydrogels,  and nanoparticles which have developed rapidly in recent years can release antimicrobial peptides stably without affecting their biological activity. It is an effective and promising method for the treatment of bone tissue infection to select appropriate drug carriers to carry antimicrobial peptides or to integrate antimicrobial peptides with antibiotics according to the characteristics, structural classification and antimicrobial mechanism. In this review, we introduce the antimicrobial mechanism of AMPs and the vectors that deliver them to locally targeted sites, summarize and discuss the advantages of antimicrobial peptides against drug-resistant pathogens, and analyze the priorities and application prospects of AMPs in the current research environment.

 

参考文献:

[1] Kandiyote NS, Avisdris T, Arnusch CJ, et al. Grafted polymer coatings enhance fouling inhibition by an antimicrobial peptide on reverse osmosis membranes[J]. Langmuir: the ACS Journal of Surfaces and Colloids, 2019, 35(5): 1935-1943.

[2] Mishra B, Reiling S, Zarena D, et al. Host defense antimicrobial peptides as antibiotics: design and application strategies[J]. Current Opinion in Chemical Biology, 2017, 38: 87-96.

[3] Magana M, Pushpanathan M, Santos AL, et al. The value of antimicrobial peptides in the age of resistance[J]. The Lancet Infectious Diseases, 2020, 20(9): e216-e230.

[4] Nakatsuji T, Gallo RL. Antimicrobial peptides: old molecules with new ideas[J]. Journal of Investigative Dermatology, 2012, 132(3): 887-895.

[5] Luong HX, Thanh TT, Tran TH. Antimicrobial peptides—advances in development of therapeutic applications[J]. Life Sciences, 2020, 260: 118407.

[6] Lazzaro BP, Zasloff M, Rolff J. Antimicrobial peptides: application informed by evolution[J]. Science, 2020, 368(6490):?eaau5480.

[7] Manrique-Moreno M, Suwalsky M, Pati?o-González E, et al. Interaction of the antimicrobial peptide ΔM3 with the?Staphylococcus aureus?membrane and molecular models[J]. Biochimica et Biophysica Acta?(BBA) -Biomembranes, 2021, 1863(2): 183498.

[8] Qiao SC, Wu DL, Li ZH, et al. The combination of multi-functional ingredients-loaded hydrogels and three-dimensional printed porous titanium alloys for infective bone defect treatment[J]. Journal of Tissue Engineering, 2020, 11(2):204173142096579.

[9] Lu HP, Liu Y, Guo J, et al. Biomaterials with antibacterial and osteoinductive properties to repair infected bone defects[J]. International Journal of Molecular Sciences, 2016, 17(3): 334.

[10] Mura M, Wang JP, Zhou YH, et al. The effect of amidation on the behaviour of antimicrobial peptides[J]. European Biophysics Journal with Biophysics Letters, 2016, 45(3): 195-207.

[11] Matsuzaki K, Murase O, Fujii N, et al. An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation[J]. Biochemistry, 1996, 35(35): 11361-11368.

[12] Shen XK, Al-Baadani MA, He HL, et al. Antibacterial and osteogenesis performances of LL37-loaded titania nanopores in vitro and in vivo[J]. International Journal of ??Nanomedicine, 2019, 14: 3043-3054.

[13] Choi H, Yang Z, Weisshaar JC. Oxidative stress induced in E. coli by the human antimicrobial peptide LL-37[J]. PLoS Pathogens, 2017, 13(6): e1006481.

[14] Epand RM, Vogel HJ. Diversity of antimicrobial peptides and their mechanisms of action[J]. Biochimica et Biophysica Acta?(BBA)-Biomembranes, 1999, 1462(1-2): 11-28.

[15] Kawauchi K, Yagihashi A, Tsuji N, et al. Human β-defensin-3 induction in H pylori-infected gastric mucosal tissues[J]. World Journal of Gastroenterology, 2006, 12(36): 5793-5797.

[16] Bayer A, Lammel J, Tohidnezhad M, et al. The antimicrobial peptide human beta-defensin-3 is induced by platelet-released growth factors in primary keratinocytes[J]. Mediators of Inflammation, 2017, 2017:6157491.

[17] Ageitos JM, Sánchez-Pérez A, Calo-Mata P, et al. Antimicrobial peptides (AMPs): ancient compounds that represent novel weapons in the fight against bacteria[J]. Biochemical?Pharmacology, 2017, 133:117-138.

[18] ?Falcao CB, Pérez-Peinado C, de la Torre BG, et al. Structural dissection of crotalicidin, a rattlesnake venom cathelicidin, retrieves a fragment with antimicrobial and antitumor activity[J]. Journal of Medicinal Chemistry, 2015, 58(21): 8553-8563.

[19] Rezaei N, Hamidabadi HG, Khosravimelal S, et al. Antimicrobial peptides-loaded smart chitosan hydrogel: release behavior and antibacterial potential against antibiotic resistant clinical isolates[J]. International Journal of Biological Macromolecules, 2020, 164: 855-862.

[20] Dijksteel GS, Ulrich MMW, Middelkoop E, et al. Review: lessons learned from clinical trials using antimicrobial peptides (AMPs)[J]. Frontiers in?Microbiology, 2021, 12:?616979.

[21] Kumar P, Kizhakkedathu JN, Straus SK. Antimicrobial peptides: diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo[J]. Biomolecules, 2018, 8(1): 4.

[22] Lee TH, Hall KN, Aguilar MI. Antimicrobial peptide structure and mechanism of action: a focus on the role of membrane structure[J]. Current Topics in Medicinal Chemistry, 2016, 16(1): 25-39.

[23] Wiener MC, White SH. Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. III. complete structure[J]. Biophysical Journal, 1992, 61(2): 434-447.

[24] Mai S, Mauger MT, Niu LN, et al. Potential applications of antimicrobial peptides and their mimics in combating caries and pulpal infections[J]. Acta Biomaterialia, 2017, 49: 16-35.

[25] Salick DA, Kretsinger JK, Pochan DJ, et al. Inherent antibacterial activity of a peptide-based beta-hairpin hydrogel[J]. Journal of the American Chemical Society, 2007, 129(47): 14793-14799.

[26] Shai Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides[J]. Biochimica et Biophysica Acta?(BBA) -Biomembranes, 1999, 1462(1-2): 55-70.

[27] He JC, Chen JJ, Hu GS, et al. Immobilization of an antimicrobial peptide on silicon surface with stable activity by click chemistry[J]. Journal of Materials Chemistry B, 2018, 6(1): 68-74.

[28] Caplin JD, García AJ.?Implantable antimicrobial biomaterials for local drug delivery in bone infection models[J]. Acta Biomaterialia, 2019, 93: 2-11.

[29] Gatin L, Mghir AS, Mouton W, et al. Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae?prosthetic joint infection[J]. International Journal of Antimicrobial Agents, 2019, 54(4): 456-462.

[30] Faber C, Stallmann HP, Lyaruu DM, et al. Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant staphylococcus aureus osteomyelitis model[J]. Antimicrobial Agents and Chemotherapy, 2005, 49(6): 2438-2444.

[31] Vaishya R, Chauhan M, Vaish A. Bone cement[J]. Journal of Clinical Orthopaedics and Trauma, 2013, 4(4): 157-163.

[32] Trzcińska Z, Bruggeman M, Ijakipour H, et al. Polydopamine linking substrate for amps: characterisation and stability on Ti6Al4V[J]. Materials (Basel), 2020, 13(17): 3714.

[33] Chen J, Shi X, Zhu Y, et al. On-demand storage and release of antimicrobial peptides using Pandora's box-like nanotubes gated with a bacterial infection-responsive polymer[J]. Theranostics, 2020, 10(1): 109-122.

[34] Chen J, Hu G, Li T, et al. Fusion peptide engineered "statically-versatile" titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration[J]. Biomaterials, 2021, 264: 120446. ?

[35] Pal P, Nguyen QC, Benton AH, et al. Drug-loaded elastin-like polypeptide-collagen hydrogels with high modulus for bone tissue engineering[J].
Macromolecular Bioscience, 2019, 19(9): e1900142.

[36] Yang GL, Huang TB, Wang Y, et al. Sustained release of antimicrobial peptide from self-assembling hydrogel enhanced osteogenesis[J]. Journal of Biomaterials Science, Polymer Edition, 2018, 29(15): 1812-1824.

[37] Bonventre PF, Gregoriandis G. Killing of intraphagocytic staphylococcus aureus by dihydrostreptomycin entrapped within liposomes[J]. Antimicrobial?Agents and Chemotherapy, 1978, 13(6): 1049-1051.

[38] He Y, Jin Y, Wang X, et al. An antimicrobial peptide-loaded gelatin/chitosan nanofibrous membrane fabricated by sequential layer-by-layer electrospinning and electrospraying techniques[J]. Nanomaterials (Basel, Switzerland), 2018, 8(5):?327.

[39] Garcia-Orue I, Gainza G, Girbau C, et al. LL37 loaded nanostructured lipid carriers (NLC): a new strategy for the topical treatment of chronic wounds[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2016, 108: 310-316.

[40] Lewies A, Wentzel JF, Jordaan A, et al. Interactions of the antimicrobial peptide nisin Z with conventional antibiotics and the use of nanostructured lipid carriers to enhance antimicrobial activity[J].?International Journal of Pharmaceutics, 2017, 526(1-2): 244-253.

[41] Uskokovi? V, Desai TA. Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. I. Preparation and drug release[J]. Journal of Biomedical Materials Research Part A, 2013, 101A(5): 1427-1436.

[42] Cong YY, Quan CY, Liu MQ, et al. Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin[J]. Journal of Biomaterials Science, Polymer Edition, 2015, 26(11): 629-643.

?

服务与反馈:
文章下载】【加入收藏
提示:您还未登录,请登录!点此登录
 
友情链接  
地址:北京安定门外安贞医院内北京生物医学工程编辑部
电话:010-64456508  传真:010-64456661
电子邮箱:llbl910219@126.com