Antimicrobial and Anti-Inflammatory Activities of MAF-1-Derived Antimicrobial Peptide Mt6 and Its D-Enantiomer D-Mt6 against Acinetobacter baumannii by Targeting Cell Membranes and Lipopolysaccharide Interaction

Kong, Delong; Huang, Xuan; Zhou, Rui; Jie, Cheng; Wang, Tao; Kong, Fanyun; You, Hongjuan; Liu, Xiangye; Adu-Amankwaah, Joseph; Guo, Guo; Zheng, Kuiyang; Wu, Jianwei; Tang, Renxian

doi:10.1128/spectrum.01312-22

Cited by 7 publications

(4 citation statements)

References 73 publications

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“…Previous investigations have shown that the neutralization of AMPs with LPS might be one of the anti-inflammatory actions of AMPs 21 , 22 . D-Mt6, designed from the hemlymphocytes of housefly larvae, showed great immunoregulatory activity against LPS-induced inflammation through its LPS neutralization and suppression of MAPK signaling 23 . In addition to the neutralization of LPS, AMPs could intervene in Toll-like receptor (TLR) signaling pathways with potent antiendotoxin properties 24 .…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial peptide 2K4L inhibits the inflammatory response in macrophages and Caenorhabditis elegans and protects against LPS-induced septic shock in mice

Ji,

Tian,

Shang

2024

Sci Rep

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Abstract2K4L is a rationally designed analog of the short α-helical peptide temporin-1CEc, a natural peptide isolated and purified from the skin secretions of the Chinese brown frog Rana chensinensis by substituting amino acid residues. 2K4L displayed improved and broad-spectrum antibacterial activity than temporin-1CEc in vitro. Here, the antibacterial and anti-inflammatory activities of 2K4L in macrophages, C. elegans and mice were investigated. The results demonstrated that 2K4L could enter THP-1 cells to kill a multidrug-resistant Acinetobacter baumannii strain (MRAB 0227) and a sensitive A. baumannii strain (AB 22933), as well as reduce proinflammatory responses induced by MRAB 0227 by inhibiting NF-κB signaling pathway. Similarly, 2K4L exhibited strong bactericidal activity against A. baumannii uptake into C. elegans, extending the lifespan and healthspan of the nematodes. Meanwhile, 2K4L alleviated the oxidative stress response by inhibiting the expression of core genes in the p38 MAPK/PMK-1 signaling pathway and downregulating the phosphorylation level of p38, thereby protecting the nematodes from damage by A. baumannii. Finally, in an LPS-induced septic model, 2K4L enhanced the survival of septic mice and decreased the production of proinflammatory cytokines by inhibiting the signaling protein expression of the MAPK and NF-κB signaling pathways and protecting LPS-induced septic mice from a lethal inflammatory response. In conclusion, 2K4L ameliorated LPS-induced inflammation both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial peptide 2K4L inhibits the inflammatory response in macrophages and Caenorhabditis elegans and protects against LPS-induced septic shock in mice

Ji,

Tian,

Shang

2024

Sci Rep

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“…Another study produced three analogues of the AMP CXCL14-C17 and the analogues were able to act on antibiotic-resistant bacteria and could have promising anti-inflammatory properties due to the inhibition of the tumor necrosis factor (TNF) and interleukin (IL-1β) [80]. Similarly, a study has been shown to produce two analogues (Mt6 and D-Mt6) of the AMP MAF-1 [81]. The analogues were observed to be stable and active against A. baumannii under many physiological settings as well as decreased TNF and IL-1β expression which suggests improved anti-inflammatory properties.…”

Section: Amps With Anti-inflammatory Propertiesmentioning

confidence: 99%

Recent Progress in the Characterization, Synthesis, Delivery Procedures, Treatment Strategies, and Precision of Antimicrobial Peptides

Bakare,

Gokul,

Niekerk

et al. 2023

IJMS

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Infectious diseases are constantly evolving to bypass antibiotics or create resistance against them. There is a piercing alarm for the need to improve the design of new effective antimicrobial agents such as antimicrobial peptides which are less prone to resistance and possess high sensitivity. This would guard public health in combating and overcoming stubborn pathogens and mitigate incurable diseases; however, the emergence of antimicrobial peptides’ shortcomings ranging from untimely degradation by enzymes to difficulty in the design against specific targets is a major bottleneck in achieving these objectives. This review is aimed at highlighting the recent progress in antimicrobial peptide development in the area of nanotechnology-based delivery, selectivity indices, synthesis and characterization, their doping and coating, and the shortfall of these approaches. This review will raise awareness of antimicrobial peptides as prospective therapeutic agents in the medical and pharmaceutical industries, such as the sensitive treatment of diseases and their utilization. The knowledge from this development would guide the future design of these novel peptides and allow the development of highly specific, sensitive, and accurate antimicrobial peptides to initiate treatment regimens in patients to enable them to have accommodating lifestyles.

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“…These AMPs drastically decrease expression of IL-β and TNF-α in LPS-stimulated macrophages. This capability is likely due to dual abilities to directly bind LPS and to inhibit the LPS-activated MAPK signaling pathways in macrophages [ 48 ]. Although this study demonstrated the mechanism by which D-Mt6 reduces inflammatory cytokine expression levels, it has not yet been confirmed how this AMP induces cell lysis and death.…”

Section: Regulatory Effect Of Amps On Macrophagesmentioning

confidence: 99%

The Contribution of Antimicrobial Peptides to Immune Cell Function: A Review of Recent Advances

Li,

Niu,

Wang

et al. 2023

Pharmaceutics

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The development of novel antimicrobial agents to replace antibiotics has become urgent due to the emergence of multidrug-resistant microorganisms. Antimicrobial peptides (AMPs), widely distributed in all kingdoms of life, present strong antimicrobial activity against a variety of bacteria, fungi, parasites, and viruses. The potential of AMPs as new alternatives to antibiotics has gradually attracted considerable interest. In addition, AMPs exhibit strong anticancer potential as well as anti-inflammatory and immunomodulatory activity. Many studies have provided evidence that AMPs can recruit and activate immune cells, controlling inflammation. This review highlights the scientific literature focusing on evidence for the anti-inflammatory mechanisms of different AMPs in immune cells, including macrophages, monocytes, lymphocytes, mast cells, dendritic cells, neutrophils, and eosinophils. A variety of immunomodulatory characteristics, including the abilities to activate and differentiate immune cells, change the content and expression of inflammatory mediators, and regulate specific cellular functions and inflammation-related signaling pathways, are summarized and discussed in detail. This comprehensive review contributes to a better understanding of the role of AMPs in the regulation of the immune system and provides a reference for the use of AMPs as novel anti-inflammatory drugs for the treatment of various inflammatory diseases.

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Antimicrobial and Anti-Inflammatory Activities of MAF-1-Derived Antimicrobial Peptide Mt6 and Its D-Enantiomer D-Mt6 against Acinetobacter baumannii by Targeting Cell Membranes and Lipopolysaccharide Interaction

Cited by 7 publications

References 73 publications

Antimicrobial peptide 2K4L inhibits the inflammatory response in macrophages and Caenorhabditis elegans and protects against LPS-induced septic shock in mice

Antimicrobial peptide 2K4L inhibits the inflammatory response in macrophages and Caenorhabditis elegans and protects against LPS-induced septic shock in mice

Recent Progress in the Characterization, Synthesis, Delivery Procedures, Treatment Strategies, and Precision of Antimicrobial Peptides

The Contribution of Antimicrobial Peptides to Immune Cell Function: A Review of Recent Advances

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