Treatment Effect of Antimicrobial Peptide LL‐1 on E.coli Infection in Vivo

doi:10.15933/j.cnki.1004-3268.2025.05.016

Journal of Henan Agricultural Sciences ›› 2025, Vol. 54 ›› Issue (5): 142-148.DOI: 10.15933/j.cnki.1004-3268.2025.05.016

• Animal Husbandry and Veterinary Medicine • Previous Articles Next Articles

Treatment Effect of Antimicrobial Peptide LL‐1 on E.coli Infection in Vivo

ZHOU Lingling^1,2，WANG Yuhang¹，SA Junmeng¹，MA Xiaoning¹，ZHANG Yuanchen³，LIAN Kaiqi^1,2，CAO Jinling⁴

（1.School of Biology and Food Engineering，Anyang Institute of Technology，Anyang 455000，China；2.Henan Joint International Research Laboratory of Veterinary Biologics Research and Application，Anyang 455000，China；3.Taihang Mountain Forest Pests Observation and Research Station of Henan Province，Linzhou 456550，China；4.College of Food Science and Engineering，Shanxi Agricultural University，Taigu 030800，China）

Received:2024-11-04 Published:2025-05-15 Online:2025-06-10

抗菌肽LL-1体内治疗大肠杆菌感染的效果

周玲玲^1,2，王宇航¹，撒俊梦¹，马小宁¹，张元臣³，连凯琪^1,2，曹瑾玲⁴

（1.安阳工学院生物与食品工程学院，河南安阳 455000；2.河南省兽用生物制品研发与应用国际联合实验室，河南安阳 455000；3.河南省太行山林业有害生物野外科学观测研究站，河南林州 456550；4.山西农业大学食品科学与工程学院，山西太谷 030800）

通讯作者: 连凯琪（1987-），男，河南驻马店人，副教授，博士，主要从事动物传染病诊断与防控研究。E-mail：liankaiqi616@163.com 曹谨玲（1979-），女，山西太谷人，教授，博士，主要从事水生生物生理与毒理研究。E-mail：caojinling7928@163.com
作者简介:周玲玲（1988-），女，河南信阳人，讲师，博士，主要从事动物传染病诊断与防控研究。E-mail：13700719135@163.com
基金资助:
河南省科技攻关计划项目（242102110073）；安阳工学院博士启动基金项目（BSJ2024005）；安阳市重点研发与推广专项（2023C01NY013）

Abstract

Abstract: The aims are to evaluate the therapeutic effect of antimicrobial peptide LL‐1 on E.coli infected mice in vivo and lay a foundation for its clinical application.Firstly，the mice model of E.coli infection was established and the optimal infection dose was determined.Mice infected with E.coli were then treated with the antimicrobial peptide LL‐1 and enrofloxacin.The effect of the treatment in vivo was evaluated according to the survival rate of mice，blood routine parameter，organ index，E.coli bacterial load，etc.And the histological changes of mice organs were detected to analyze the influence of antimicrobial peptide LL‐1 on mice.The results showed that the optimal infection concentration for establishing a mouse model of E.coli infection was 108 cfu/mL.The survival rate of the mice in the positive control group（POS group）was 30%，while the treatment group mice with 80 mg/kg LL‐1（PEPJ group）reached 100%.Compared with the POS group，the liver index of the PEPJ group was extremely significantly increased，and the spleen index was significantly decreased，and the amount of E.coli in the spleen and lung were significantly decreased；Among the main parameters of blood routine in mice，the intermediate cell count of PEPJ group was significantly reduced；HE staining showed that LL‐1 significantly alleviated multi‐organ（liver，spleen，kidney，lung）lesions，inflammatory cell infiltration，and intestinal villus shedding induced by E.coli infection.And the overall therapeutic effect of 80 mg/kg LL‐1 on mice infected with E.coli was better than that of the treatment group with 200 mg/kg enrofloxacin.In conclusion，the antimicrobial peptide LL‐1 has a good effect against E.coli in mice，which lays a foundation for further study of the role and clinical application of the antimicrobial peptide in the future.

Key words: Antimicrobial peptide, E.coli, In vivo antibacterium, Infection model in mice, Clinical application

摘要： 为了评估抗菌肽LL-1对大肠杆菌感染小鼠的体内治疗效果，为抗菌肽LL-1的临床应用奠定基础，首先建立大肠杆菌感染小鼠模型，确定最佳感染剂量；然后使用抗菌肽LL-1和恩诺沙星分别对大肠杆菌感染的小鼠模型进行治疗，根据小鼠存活率、血常规参数、器官指数、内脏载菌量等指标多方面评价抗菌肽LL-1体内治疗效果，并通过检测小鼠脏器组织学变化来分析抗菌肽LL-1对小鼠的影响。结果表明，建立大肠杆菌感染小鼠模型的最佳感染浓度为10⁸ cfu/mL。阳性对照组（POS组）小鼠存活率为30%，80 mg/kg LL-1治疗组（PEPJ组）小鼠的存活率达到100%；与POS组相比，PEPJ组的小鼠肝脏指数极显著升高，脾脏指数显著降低，脾脏、肺脏大肠杆菌载菌量极显著降低；在小鼠血常规主要参数中，PEPJ组中间细胞计数显著减少；HE染色结果显示，LL-1显著缓解了大肠杆菌感染引起的多器官（肝、脾、肾、肺）病变、炎性细胞浸润，以及肠道绒毛脱落。80 mg/kg LL-1对大肠杆菌感染小鼠的总体治疗效果优于200 mg/kg 恩诺沙星治疗组。综上，抗菌肽LL-1对小鼠具有良好的体内抗大肠杆菌作用，为今后更深入研究该抗菌肽的作用及临床应用奠定基础。

关键词: 抗菌肽, 大肠杆菌, 体内抗菌, 小鼠感染模型, 临床应用

CLC Number:

S855.1

ZHOU Lingling, WANG Yuhang, SA Junmeng, MA Xiaoning, ZHANG Yuanchen, LIAN Kaiqi, CAO Jinling. Treatment Effect of Antimicrobial Peptide LL‐1 on E.coli Infection in Vivo[J]. Journal of Henan Agricultural Sciences, 2025, 54(5): 142-148.

周玲玲, 王宇航, 撒俊梦, 马小宁, 张元臣, 连凯琪, 曹瑾玲. 抗菌肽LL-1体内治疗大肠杆菌感染的效果[J]. 河南农业科学, 2025, 54(5): 142-148.

Figures/Tables 6

References

［1］COUVREUR P， FATTAL E， ANDREMONT A.Liposomes and nanoparticles in the treatment of intracellular bacterial infections［J］.Pharmaceutical Research，1991，8（9）：1079‑1086.

［2］BUCCINI D F，CARDOSO M H，FRANCO O L.Antimicrobial peptides and cell‑penetrating peptides for treating intracellular bacterial infections［J］.Frontiers in Cellular and Infection Microbiology，2021，10：612931.

［3］PAITAN Y.Current trends in antimicrobial resistance of Escherichia coli［J］.Current Topics in Microbiology and Immunology，2018，416：181‑211.

［4］WANG X，WANG X M，TENG D，et al. Increased intracellular activity of MP1102 and NZ2114 against Staphylococcus aureus in vitro and in vivo［J］. Scientific Reports，2018，8（1）：4204.

［5］YANG L，SUN Y W，XU Y Z，et al. Antibacterial peptide BSN‑37 kills extra‑ and intra‑cellular Salmonella enterica serovar typhimurium by a nonlytic mode of action［J］.Frontiers in Microbiology，2020，11：174.

［6］RIDYARD K E，OVERHAGE J. The potential of human peptide LL‑37 as an antimicrobial and anti‑biofilm agent［J］. Antibiotics，2021，10（6）：650.

［7］ NADAR S，KHAN T，PATCHING S G，et al.Development of antibiofilm therapeutics strategies to overcome antimicrobial drug resistance［J］.Microorganisms，2022，10（2）：303.

［8］WANG J R，MA K，RUAN M S，et al.A novel cecropin B‑derived peptide with antibacterial and potential anti‑inflammatory properties［J］.PeerJ，2018，6：e5369.

［9］GU H，KATO T，KUMETA H，et al. Three‑dimensional structure of the antimicrobial peptide cecropin P1 in dodecylphosphocholine micelles and the role of the C‑terminal residues［J］. ACS Omega，2022，7（36）：31924‑31934.

［10］NIKAWA H，FUKUSHIMA H，MAKIHIRA S，et al.Fungicidal effect of three new synthetic cationic peptides against Candida albicans［J］. Oral Diseases，2004，10（4）：221‑228.

［11］李鹏，王俊茹，冯丽丽，等. 艾草固态发酵工艺优化及其对PRRSV抑制作用研究［J］. 河南农业科学，2024，53（6）：128‑137.

LI P，WANG J R，FENG L L，et al. Optimization of Solid‑state Fermentation Process of Artemisia argyi and Its Inhibitory Effect on PRRSV［J］.Journal of Henan Agricultural Sciences，2024，53（6）：128‑137.

［12］DENANI C B，REAL‑HOHN A，DE CARVALHO C A M，et al. Lactoferrin affects rhinovirus B‑14 entry into H1‑HeLa cells［J］. Archives of Virology，2021，166（4）：1203‑1211.

［13］MARCHETTI M，SUPERTI F，AMMENDOLIA M G，et al. Inhibition of poliovirus type 1 infection by iron‑，manganese‑ and zinc‑saturated lactoferrin［J］. Medical Microbiology and Immunology，1999，187（4）：199‑204. ［14］MCCANN K B，LEE A，WAN J，et al. The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus（a norovirus surrogate）and poliovirus to infect cell cultures［J］.Journal of Applied Microbiology，2003，95（5）：1026‑1033.

［15］LIN T Y，CHU C，CHIU C H. Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro［J］.The Journal of Infectious Diseases，2002，186（8）：1161‑1164.

［16］WENG T Y，CHEN L C，SHYU H W，et al. Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells［J］. Antiviral Research，2005，67 （1）：31‑37.

［17］PIETRANTONI A，AMMENDOLIA M G，TINARI A，et al. Bovine lactoferrin peptidic fragments involved in inhibition of Echovirus 6 in vitro infection［J］.Antiviral Research，2006，69（2）：98‑106.

［18］冯丽丽. 枯草芽孢杆菌在养殖生产中的应用及对动物肠道健康的影响研究进展［J/OL］. 河南农业科学，2024［2024‑11‑01］. http：//kns.cnki.net/kcms/detail/41.1092.S.20240903.1812.002.html.

FENG L L. Research Progress on the Application of Bacillus subtilis in Aquaculture Production and Its Impact on Animal Intestinal Health［J/OL］. Journal of Henan Agricultural Sciences，2024［2024‑11‑01］.http：//kns.cnki.net/kcms/detail/41.1092.S.20240903.1812.002.html.

［19］HAO S H，SHI W H，CHEN L J，et al.CATH‑2‑derived antimicrobial peptide inhibits multidrug‑resistant Escherichia coli infection in chickens［J］.Frontiers in Cellular and Infection Microbiology，2024，14：1390934. ［20］ZHU C L，BAI Y L，XIA X J，et al. Effects of the antimicrobial peptide mastoparan X on the performance，permeability and microbiota populations of broiler chickens［J］. Animals，2022，12（24）：3462.

［21］SHEN S S，REN F，HE J P，et al. Recombinant antimicrobial peptide OaBac5mini alleviates inflammation in pullorum disease chicks by modulating TLR4/MyD88/NF‑κB pathway［J］. Animals，2023，13（9）：1515.

［22］陈忠宜. 枯草芽孢杆菌J-15代谢产物治疗小鼠白色念珠菌感染及提高机体免疫力的作用［D］.乌鲁木齐：新疆师范大学，2021.

CHEN Z Y. Effects of Metabolites of Bacillus subtilis J‑15 on Candida albicans infection in mice and improving immunity［D］. Urumqi：Xinjiang Normal University，2021.

［23］DUARTE‑MATA D I，SALINAS‑CARMONA M C.Antimicrobial peptides’immune modulation role in intracellular bacterial infection ［J］. Frontiers in Immunology，2023，14：1119574.

［24］FENG J S，WANG L，XIE Y S，et al. Effects of antimicrobial peptide cathelicidin‑BF on diarrhea controlling，immune responses，intestinal inflammation and intestinal barrier function in piglets with postweaning diarrhea［J］.International Immunopharmacology，2020，85：106658.

［25］WU D，FU L L，WEN W Z，et al. The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production［J］. Journal of Animal Science and Biotechnology，2022，13（1）：141.

［26］LIU S L，WANG S D，LIU X W，et al. Effects of dietary antimicrobial peptides on intestinal morphology，antioxidant status，immune responses，microbiota and pathogen disease resistance in grass carp Ctenopharyngodon idellus［J］. Microbial Pathogenesis，2022，165：105386.

[1]	MAO Guotao, LIU Qian, WANG Fangyuan, SU Lijuan, ZHANG Hongsen, SONG Andong. Heterologous Expression and Characterization of the β-glucosidase RpBgl7 from Reticulitermes perilucifugus [J]. Journal of Henan Agricultural Sciences, 2020, 49(7): 68-74.
[2]	ZHANG Suling, WU Peng, YUE Ya’nan, BAI Chenyu, HAO Liying, LI Xiangdong, PANG Wenqiang, TIAN Kegong. Expression and Purification of MGF505-5R Protein of African Swine Fever Virus [J]. Journal of Henan Agricultural Sciences, 2020, 49(10): 130-136.

Treatment Effect of Antimicrobial Peptide LL‐1 on E.coli Infection in Vivo

抗菌肽LL-1体内治疗大肠杆菌感染的效果

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 6

References

Related Articles 2

Recommended Articles

Metrics