scholarly journals A New Era of Antibiotics: The Clinical Potential of Antimicrobial Peptides

2020 ◽  
Vol 21 (19) ◽  
pp. 7047 ◽  
Author(s):  
Katrina Browne ◽  
Sudip Chakraborty ◽  
Renxun Chen ◽  
Mark DP Willcox ◽  
David StClair Black ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Therapeutic Potential ◽  
Innate Immune ◽  
Antimicrobial Compound ◽  
Peptide Backbone ◽  
New Era ◽  
Evolutionarily Conserved ◽  
Clinical Potential ◽  
Activity Design

Antimicrobial resistance is a multifaceted crisis, imposing a serious threat to global health. The traditional antibiotic pipeline has been exhausted, prompting research into alternate antimicrobial strategies. Inspired by nature, antimicrobial peptides are rapidly gaining attention for their clinical potential as they present distinct advantages over traditional antibiotics. Antimicrobial peptides are found in all forms of life and demonstrate a pivotal role in the innate immune system. Many antimicrobial peptides are evolutionarily conserved, with limited propensity for resistance. Additionally, chemical modifications to the peptide backbone can be used to improve biological activity and stability and reduce toxicity. This review details the therapeutic potential of peptide-based antimicrobials, as well as the challenges needed to overcome in order for clinical translation. We explore the proposed mechanisms of activity, design of synthetic biomimics, and how this novel class of antimicrobial compound may address the need for effective antibiotics. Finally, we discuss commercially available peptide-based antimicrobials and antimicrobial peptides in clinical trials.

scholarly journals Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants

2019 ◽  
Vol 12 (6) ◽  
pp. dmm037721 ◽  
Author(s):  
Mayo Araki ◽  
Massanori Kurihara ◽  
Suzuko Kinoshita ◽  
Rie Awane ◽  
Tetsuya Sato ◽  
...  
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Innate Immune

scholarly journals Recent advances in understanding inhibitor of apoptosis proteins

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1889 ◽  
Author(s):  
Najoua Lalaoui ◽  
David Lawrence Vaux
Keyword(s):  
Innate Immune System ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Caspase Activation ◽  
Recent Advances ◽  
Iap Antagonist ◽  
Apoptosis Proteins

The inhibitor of apoptosis proteins (IAPs) are a family of proteins that were chiefly known for their ability to inhibit apoptosis by blocking caspase activation or activity. Recent research has shown that cellular IAP1 (cIAP1), cIAP2, and X-linked IAP (XIAP) also regulate signaling by receptors of the innate immune system by ubiquitylating their substrates. These IAPs thereby act at the intersection of pathways leading to cell death and inflammation. Mutation of IAP genes can impair tissue homeostasis and is linked to several human diseases. Small-molecule IAP antagonists have been developed to treat certain malignant, infectious, and inflammatory diseases. Here, we will discuss recent advances in our understanding of the functions of cIAP1, cIAP2, and XIAP; the consequences of their mutation or dysregulation; and the therapeutic potential of IAP antagonist drugs.

scholarly journals Bacterial strategies of resistance to antimicrobial peptides

2016 ◽  
Vol 371 (1695) ◽  
pp. 20150292 ◽  
Author(s):  
Hwang-Soo Joo ◽  
Chih-Iung Fu ◽  
Michael Otto
Keyword(s):  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Evolutionary Ecology ◽  
Resistance Mechanisms ◽  
Innate Immune ◽  
Surface Structures ◽  
Antimicrobial Drugs ◽  
Bacterial Surface ◽  
Membrane Charge ◽  
Virulence Potential

Antimicrobial peptides (AMPs) are a key component of the host's innate immune system, targeting invasive and colonizing bacteria. For successful survival and colonization of the host, bacteria have a series of mechanisms to interfere with AMP activity, and AMP resistance is intimately connected with the virulence potential of bacterial pathogens. In particular, because AMPs are considered as potential novel antimicrobial drugs, it is vital to understand bacterial AMP resistance mechanisms. This review gives a comparative overview of Gram-positive and Gram-negative bacterial strategies of resistance to various AMPs, such as repulsion or sequestration by bacterial surface structures, alteration of membrane charge or fluidity, degradation and removal by efflux pumps. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.

Role of Toll-like receptors in liver health and disease

2011 ◽  
Vol 121 (10) ◽  
pp. 415-426 ◽  
Author(s):  
Ruth Broering ◽  
Mengji Lu ◽  
Joerg F. Schlaak
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Evolutionarily Conserved ◽  
Liver Health ◽  
Health And Disease ◽  
Molecular Patterns

TLRs (Toll-like receptors), as evolutionarily conserved germline-encoded pattern recognition receptors, have a crucial role in early host defence by recognizing so-called PAMPs (pathogen-associated molecular patterns) and may serve as an important link between innate and adaptive immunity. In the liver, TLRs play an important role in the wound healing and regeneration processes, but they are also involved in the pathogenesis and progression of various inflammatory liver diseases, including autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, fibrogenesis, and chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection. Hepatitis viruses have developed different evading strategies to subvert the innate immune system. Thus recent studies have suggested that TLR-based therapies may represent a promising approach in the treatment in viral hepatitis. The present review focuses on the role of the local innate immune system, and TLRs in particular, in the liver.

Cytokine function of heat shock proteins

2004 ◽  
Vol 286 (4) ◽  
pp. C739-C744 ◽  
Author(s):  
Min-Fu Tsan ◽  
Baochong Gao
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Innate Immune System ◽  
Therapeutic Potential ◽  
Innate Immune ◽  
Heat Sensitivity ◽  
Receptor Complex ◽  
Shock Proteins ◽  
Antigen Presenting ◽  
Tlr4 Receptor

Extensive work in the last 10 years has suggested that heat shock proteins (HSPs) may be potent activators of the innate immune system. It has been reported that Hsp60, Hsp70, Hsp90, and gp96 are capable of inducing the production of proinflammatory cytokines by the monocyte-macrophage system and the activation and maturation of dendritic cells (antigen-presenting cells) in a manner similar to the effects of lipopolysaccharide (LPS) and bacterial lipoprotein, e.g., via CD14/Toll-like receptor2 (TLR2) and CD14/TLR4 receptor complex-mediated signal transduction pathways. However, recent evidence suggests that the reported cytokine effects of HSPs may be due to the contaminating LPS and LPS-associated molecules. The reasons for previous failure to recognize the contaminant(s) as being responsible for the reported HSP cytokine effects include failure to use highly purified, low-LPS preparations of HSPs; failure to recognize the heat sensitivity of LPS; and failure to consider contaminant(s) other than LPS. Thus it is essential that efforts should be directed to conclusively determine whether the reported HSP cytokine effects are due to HSPs or to contaminant(s) present in the HSP preparations before further exploring the implication and therapeutic potential of the putative cytokine function of HSPs.

scholarly journals Antimicrobial peptides: key components of the innate immune system

2011 ◽  
Vol 32 (2) ◽  
pp. 143-171 ◽  
Author(s):  
Mukesh Pasupuleti ◽  
Artur Schmidtchen ◽  
Martin Malmsten
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Innate Immune

scholarly journals Mini Review on Antimicrobial Peptides, Sources, Mechanism and Recent Applications

2019 ◽  
Vol 27 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Jaspreet Kaur Boparai ◽  
Pushpender Kumar Sharma
Keyword(s):  
Antimicrobial Peptides ◽  
Biological Diversity ◽  
Therapeutic Potential ◽  
High Specificity ◽  
New Era ◽  
Therapeutic Drugs ◽  
Therapeutic Peptides ◽  
Low Toxicity ◽  
Pharmaceutical Industries ◽  
Micro Organisms

Antimicrobial peptides in recent years have gained increased interest among scientists, health professionals and the pharmaceutical companies owing to their therapeutic potential. These are low molecular weight proteins with broad range antimicrobial and immuno modulatory activities against infectious bacteria (Gram positive and Gram negative), viruses and fungi. Inability of micro-organisms to develop resistance against most of the antimicrobial peptide has made them as an efficient product which can greatly impact the new era of antimicrobials. In addition to this these peptides also demonstrates increased efficacy, high specificity, decreased drug interaction, low toxicity, biological diversity and direct attacking properties. Pharmaceutical industries are therefore conducting appropriate clinical trials to develop these peptides as potential therapeutic drugs. More than 60 peptide drugs have already reached the market and several hundreds of novel therapeutic peptides are in preclinical and clinical development. Rational designing can be used further to modify the chemical and physical properties of existing peptides. This mini review will discuss the sources, mechanism and recent therapeutic applications of antimicrobial peptides in treatment of infectious diseases.

The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides

2016 ◽  
Vol 397 (9) ◽  
pp. 939-945 ◽  
Author(s):  
Mohammad Reza Bolouri Moghaddam ◽  
Miray Tonk ◽  
Christine Schreiber ◽  
Denise Salzig ◽  
Peter Czermak ◽  
...  
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Inhibitory Concentration ◽  
Galleria Mellonella ◽  
Micrococcus Luteus ◽  
Innate Immune ◽  
Sublethal Dose ◽  
E Coli ◽  
Cecropin A

Abstract Antimicrobial peptides (AMPs) are ubiquitous components of the insect innate immune system. The model insect Galleria mellonella has at least 18 AMPs, some of which are still uncharacterized in terms of antimicrobial activity. To determine why G. mellonella secretes a repertoire of distinct AMPs following an immune challenge, we selected three different AMPs: cecropin A (CecA), gallerimycin and cobatoxin. We found that cobatoxin was active against Micrococcus luteus at a minimum inhibitory concentration (MIC) of 120 μm, but at 60 μm when co-presented with 4 μm CecA. In contrast, the MIC of gallerimycin presented alone was 60 μm and the co-presentation of CecA did not affect this value. Cobatoxin and gallerimycin were both inactive against Escherichia coli at physiological concentrations, however gallerimycin could potentiate the sublethal dose of CecA (0.25 μm) at a concentration of 30 μm resulting in 100% lethality. The ability of gallerimycin to potentiate the CecA was investigated by flow cytometry, revealing that 30 μm gallerimycin sensitized E. coli cells by inducing membrane depolarization, which intensified the otherwise negligible effects of 0.25 μm CecA. We therefore conclude that G. mellonella maximizes the potential of its innate immune response by the co-presentation of different AMPs that become more effective at lower concentrations when presented simultaneously.

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