MOLECULES
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2023
·Vol. 28
·期 5
·2082
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IF 4.6
Shuocun Wang,Liming Fan,Hanyu Pan,Yingying Li,Xin Zhao,Yan Qiu,Yiming Lu
The abuse of antibiotics and lack of new antibacterial drugs has led to the emergence of superbugs that raise fears of untreatable infections. The Cathelicidin family of antimicrobial peptide (AMP) with varying antibacterial activities and safety is considered to be a promising alternative to conventional antibiotics. In this study, we investigated a novel Cathelicidin peptide named Hydrostatin-AMP2 from the sea snakeHydrophis cyanocinctus. The peptide was identified based on gene functional annotation of theH. cyanocinctusgenome and bioinformatic prediction. Hydrostatin-AMP2 showed excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria, including standard and clinical Ampicillin-resistant strains. The results of the bacterial killing kinetic assay demonstrated that Hydrostatin-AMP2 had faster antimicrobial action than Ampicillin. Meanwhile, Hydrostatin-AMP2 exhibited significant anti-biofilm activity including inhibition and eradication. It also showed a low propensity to induce resistance as well as low cytotoxicity and hemolytic activity. Notably, Hydrostatin-AMP2 apparently decreased the production of pro-inflammatory cytokines in the LPS-induced RAW264.7 cell model. To sum up, these findings indicate that Hydrostatin-AMP2 is a potential peptide candidate for the development of new-generation antimicrobial drugs fighting against antibiotic-resistant bacterial infections.Keywords:bacterial resistance;Cathelicidin;antimicrobial peptide;sea snake;infection;bioinformatic prediction
研究领域:
微生物学
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药理学
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免疫学
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生物信息学
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DOI
PubMed
高影响因子
Frontiers in Immunology
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2019
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IF 4.716
Zong Xin,Cao Xiaoxuan,Wang Hong,Xiao Xiao,Wang Yizhen,Lu Zeqing
The molecular mechanisms underlying the cellular uptake of long-chain fatty acids and the regulation of this process have been debated in recent decades. Here, we established an intestinal barrier dysfunction model in mice and Caco2 cell line by Lipopolysaccharide (LPS), and evaluated the fatty acid uptake capacity of the intestine. We found that LPS stimulation restricted the absorption of long chain fatty acid (LCFA), while Cathelicidin-WA (CWA) pretreatment facilitated this physiological process. At the molecular level, our results demonstrated that the stimulatory effects of CWA on intestinal lipid absorption were dependent on cluster determinant 36 and fatty acid transport protein 4, but not fatty acid–binding protein. Further, an enhanced intestinal barrier was observed in vivo and in vitro when CWA alleviated the fatty acid absorption disorder induced by LPS stimulation. Mechanistically, peroxisome proliferator-activated receptor (PPAR-γ) signaling was considered as a key pathway for CWA to enhance LCFA absorption and barrier function. Treatment with a PPAR-γ inhibitor led to impaired intestinal barrier function and suppressed LCFA uptake. Moreover, once PPAR-γ signaling was blocked, CWA pretreatment could not maintain the stability of the intestinal epithelial cell barrier or LCFA uptake after LPS stimulation. Collectively, these findings suggested that PPAR-γ may serve as a target for specific therapies aimed at alleviating fatty acid uptake disorder, and CWA showed considerable potential as a new PPAR-γ agonist to strengthen intestinal barrier function against fatty acid malabsorption.
研究领域:
胃肠病学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
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2020
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IF 4.133
Yan Wu,Yacheng Zhang,Jie Zhang,Tingting Zhai,Jingping Hu,Hairong Luo,Haiyan Zhou,Qinghai Zhang,Zhiguang Zhou,Feng Liu
Aims The antimicrobial peptide cathelicidin ( Camp ) has multifunctional immunomodulatory activities. However, its roles in inflammation-related myocardial ischemia/reperfusion (MI/R) injury remain unclear. Methods and results In this study, adult male C57BL/6 wild-type (WT) mice were subjected to MI/R injury by left anterior descending coronary artery ligation for 45 min followed by 3 or 24 h of reperfusion . An abundant cardiac expression of cathelicidin was observed during ischemia and reperfusion, which was mainly derived from heart-infiltrating neutrophils . Knockout of Camp in mice reduced MI/R-induced myocardial inflammation , infarct size, and circulating cTnI levels (an indicator of heart damage). CRAMP (the mature form of murine cathelicidin) administration of WT mice immediately before MI/R exerted detrimental effects on the reperfused heart. CRAMP exacerbates MI/R injury via a TLR4 and P2X 7 R/NLRP3 inflammasome-dependent mechanism, since I/R-induced myocardial infarction was reserved by inhibition of TLR4, P2X 7 R, or NLRP3 inflammasome in CRAMP-treated WT mice. Depletion of neutrophils before MI/R abrogated the amplification of infarct size in CRAMP-treated WT mice. Heart-infiltrating neutrophils were found to be one of major cellular sources of myocardial IL-1β (a “first line” pro-inflammatory cytokine) at the early stage of MI/R. At this stage, CRAMP administration just before MI/R induced pro-IL-1β protein expression in heart-infiltrating neutrophils, but not in non-neutrophils. In vitro experiments showed that LL-37 (the mature form of human cathelicidin) treatment promotes the processing and secretion of IL-1β from human neutrophils via stimulating TLR4 signaling and P2X 7 R/NLRP3 inflammasome. Conclusions Our findings reveal that, at the early stage of MI/R, neutrophil-derived cathelicidin plays an injurious role in the heart. Cathelicidin aggravates MI/R injury by over-activating TLR4 signaling and P2X 7 R/NLRP3 inflammasome in heart-infiltrating neutrophils, which leads to the excessive secretion of IL-1β and subsequent inflammatory injury .
研究领域:
心脏病学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
Toxins
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2019
·Vol. 11
·期 7
·379
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IF 3.895
Yaqun Fang,Xiaoqin He,Pengcheng Zhang,Chuanbin Shen,James Mwangi,Cheng Xu,Guoxiang Mo,Ren Lai,Zhiye Zhang
Antimalarial drug resistance is an enormous global threat. Recently, antimicrobial peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed strong suppression of blood stagePlasmodium falciparum(P. falciparum) with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity againstPlasmodium berghei(P. berghei) in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment duringP. bergheiinfection. Furthermore, by employing inhibitors against glycolysis and oxidative phosphorylation in erythrocytes, LZ1 specifically inhibited adenosine triphosphate (ATP) production in parasite-infected erythrocyte by selectively inhibiting the pyruvate kinase activity. In conclusion, the present study demonstrates that LZ1 is a potential candidate for novel antimalarials development.Keywords:antimicrobial peptide;malaria;cytokine;pyruvate kinase;ATPKey Contribution:This study reports a synthetic peptide derived from the snake cathelicidin, named LZ1. LZ1 shows both in vitro and in vivo antimalarial activity by limiting ATP production in parasite-infected erythrocyte.
研究领域:
药理学
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传染病学
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分子生物学
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DOI
PubMed
高影响因子
VETERINARY RESEARCH
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2026
·Vol. 57
·期 1
·175
·
IF 3.8
Jiang Luyao,Yang Fan,Wu Jiayan,Li Zhengliang,Zhu Xiemin,Pan Hao,Zhang Shaotong,Pan Haochun,Wang Hang,Yao Jingting,Yan Ping,Gao Qingqing,Huan Changchao,Gao Song,Jiao Xinan,Liu Xiufan
Host defense peptides (HDPs) possess both direct bacteriocidal and immunomodulatory activities. In this study, chicken cathelicidin-1 (cCATH-1) and chicken cathelicidin-3 (cCATH-3) were selected based on their markedly different minimum inhibitory concentrations (MICs) against avian pathogenic Escherichia coli (APEC) strains, with MICs of cCATH-1 being 4- to 16-fold lower than those of cCATH-3. However, following intraperitoneal challenge with APEC strain E058 (4 × 10⁶ CFU/mouse), 80% of cCATH-3 treated mice survived while 20% of cCATH-1 treated mice survived. Flow cytometry (FC) revealed significantly lower peripheral blood Ly6C high monocytes but higher peritoneal Ly6C high macrophages in cCATH-3-treated mice at 4 and 8 h post-treatment. Peritoneal CCL3 secretion was significantly upregulated in cCATH-3 treated mice at 8 h post-treatment. Upon knockout of macrophages, the protection of cCATH-3 in mice against APEC E058 challenge was markedly abolished. In vitro, peritoneal macrophages treated with cCATH-3 showed stronger bacteriocidal activity than those treated with cCATH-1. Mouse CCL-3 (mCCL3)-specific antibody neutralize the effect of mCCL3 on macrophages chemotaxis in vitro. mCCL3-specific antibody administration resulted in 0% survival in cCATH-3-treated mice versus 60% survival in cCATH-3-treated mice administered with mock antibody, while cCATH-1-treated mice showed 0% survival administered with either mCCL3-specific antibody or mock antibody after APEC E058 strain challenge. In summary, cCATH-3 provides robust protection against APEC infection compared with cCATH-1 in mice, partially through CCL3-mediated macrophage chemotaxis and enhanced bacteriocidal activity in activated macrophages, revealing a novel mechanism of avian cathelicidins and supporting HDPs as alternatives to antibiotics for controlling avian colibacillosis.
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DOI
高影响因子
Computational and Structural Biotechnology Journal
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2024
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IF 4.4
Jian Wang,Meina Zhang,Chao Li,Mengyuan Liu,Yixin Qi,Xiaolin Xie,Changlin Zhou,Lingman Ma
Antimicrobial peptides are promising therapeutic agents for treating drug-resistant bacterial disease due to their broad-spectrum antimicrobial activity and decreased susceptibility to evolutionary resistance. In this study, three novel cathelicidin antimicrobial peptides were identified from Thamnophis sirtalis , Balaenoptera musculus , and Lipotes vexillifer by protein database mining and sequence alignment and were subsequently named TS-CATH, BM-CATH, and LV-CATH, respectively. All three peptides exhibited satisfactory antibacterial activity and broad antibacterial spectra against clinically isolated E. coli , P. aeruginosa , K. pneumoniae , and A. baumannii in vitro . Among them, TS-CATH displayed the best antimicrobial/bactericidal activity, with a rapid elimination efficiency against the tested drug-resistant gram-negative bacteria within 20 minutes, and exhibited the lowest cytotoxicity toward mammalian cells. Furthermore, TS-CATH effectively enhanced the survival rate of mice with ceftazidime-resistant E. coli bacteremia and promoted wound healing in meropenem-resistant P. aeruginosa infection. These results were achieved through the eradication of bacterial growth in target organs and wounds, further inhibiting the systemic dissemination of bacteria and the inflammatory response. TS-CATH exhibited direct antimicrobial activity by damaging the inner and outer membranes, resulting in leakage of the bacterial contents at super-MICs. Moreover, TS-CATH disrupted the bacterial respiratory chain, which inhibited ATP synthesis and induced ROS formation, significantly contributing to its antibacterial efficacy at sub-MICs. Overall, TS-CATH has potential for use as an antibacterial agent.
研究领域:
微生物学
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药理学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
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