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Antimicrobial Peptides and Immunology

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (28 November 2022) | Viewed by 24222

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Dr. Elena Chaves-Pozo

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Guest Editor

Centro Oceanográfico de Murcia (COMU-IEO), CSIC, Carretera de la Azohía s/n, Puerto de Mazarrón, 30860 Murcia, Spain
Interests: immune-reproductive responses; marine fish; viral transmission through the gonad; endocrine disruption
Special Issues, Collections and Topics in MDPI journals

Dr. Alberto Cuesta

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Department of Cell Biology and Histology, Faculty of Biology, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100 Murcia, Spain
Interests: fish, immunology; virus, AMPs; toxicology; cell lines; vaccines; aquaculture; biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial peptides (AMPs) have improved our capacity to generate novel treatments against infectious disease of variable pathogens such as bacteria, viruses, fungi, and parasites because of their ability to disrupt their membranes or capsid and kill them directly. In addition, they do not generate resistance and are critical factors in innate immune response since they are key players in the regulation of several immune responses, including the specific response. Thus, antimicrobial peptides are promising candidates as potential therapeutic molecules, although their molecular mechanisms of action are not completely understood today. This issue invites studies identifying novel and known AMPs in the animal kingdom and in human beings; characterizing their immunomodulatory potential and mechanisms at the cellular and molecular level, as well as their antimicrobial role against dangerous pathogens for different hosts; and exploring AMPs’ biological use in clinical therapies in human health. The outcome of the studies collected here will represent a further step in our comprehension of the innate immune system of multiple organisms and the identification of novel treatments for infective diseases with a focus on AMPs.

Dr. Elena Chaves-Pozo
Dr. Alberto Cuesta
Guest Editors

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Keywords

antimicrobial peptides
immune regulation
macrophages
mast cells
granulocytes
neutrophiles
chemiotaxis
G-protein couple membrane receptors
inmunoadjuvants
T cell proliferation
cytokine regulation

Published Papers (9 papers)

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Research

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12 pages, 2616 KiB

Open AccessArticle

A Designed Host Defense Peptide for the Topical Treatment of MRSA-Infected Diabetic Wounds

by Alex Vargas, Gustavo Garcia, Kathryn Rivara, Kathryn Woodburn, Louis Edward Clemens and Scott I. Simon

Int. J. Mol. Sci. 2023, 24(3), 2143; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032143 - 21 Jan 2023

Cited by 3 | Viewed by 1702

Abstract

Diabetes mellitus is a chronic disease characterized by metabolic dysregulation which is frequently associated with diabetic foot ulcers that result from a severely compromised innate immune system. The high levels of blood glucose characteristic of diabetes cause an increase in circulating inflammatory mediators, which accelerate cellular senescence and dampen antimicrobial activity within dermal tissue. In diabetic wounds, bacteria and fungi proliferate in a protective biofilm forming a structure that a compromised host defense system cannot easily penetrate, often resulting in chronic infections that require antimicrobial intervention to promote the healing process. The designed host defense peptide (dHDP) RP557 is a synthesized peptide whose sequence has been derived from naturally occurring antimicrobial peptides (AMPs) that provide the first line of defense against invading pathogens. AMPs possess an amphipathic α-helix or β-sheet structure and a net positive charge that enables them to incorporate into pathogen membranes and perturb the barrier function of Gram-positive and Gram-negative bacteria along with fungi. The capacity of skin to resist infections is largely dependent upon the activity of endogenous AMPs that provided the basis for the design and testing of RP557 for the resolution of wound infections. In the current study, the topical application of RP557 stopped bacterial growth in the biofilm of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infected wounds on the flanks of clinically relevant diabetic TALLYHO mice. Topical application of RP557 reduced bacterial load and accelerated wound closure, while wound size in control diabetic mice continued to expand. These studies demonstrate that RP557 reduces or eliminates an infection in its biofilm and restores wound-healing capacity. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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22 pages, 10362 KiB

Open AccessArticle

Analysis of the Toll and Spaetzle Genes Involved in Toll Pathway-Dependent Antimicrobial Gene Induction in the Red Flour Beetle, Tribolium castaneum (Coleoptera; Tenebrionidae)

by Daiki Kato, Ken Miura and Kakeru Yokoi

Int. J. Mol. Sci. 2023, 24(2), 1523; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021523 - 12 Jan 2023

Cited by 3 | Viewed by 1739

Abstract

Insects rely only on their innate immune system to protect themselves from pathogens. Antimicrobial peptide (AMP) production is the main immune reaction in insects. In Drosophila melanogaster, the reaction is regulated mainly by the Toll and immune deficiency (IMD) pathways. Spaetzle proteins, activated by immune signals from upstream components, bind to Toll proteins, thus, activating the Toll pathway, which in turn, induces AMP genes. Previous studies have shown the difference in immune systems related to Toll and IMD pathways between D. melanogaster and Tribolium castaneum. In T. castaneum, nine Toll and seven spaetzle (spz) genes were identified. To extend our understanding of AMP production by T. castaneum, we conducted functional assays of Toll and spaetzle genes related to Toll-pathway-dependent AMP gene expression in T. castaneum under challenge with bacteria or budding yeast. The results revealed that Toll3 and Toll4 double-knockdown and spz7 knockdown strongly and moderately reduced the Toll-pathway-dependent expression of AMP genes, respectively. Moreover, Toll3 and Toll4 double-knockdown pupae more rapidly succumbed to entomopathogenic bacteria than the control pupae, but spz7 knockdown pupae did not. The results suggest that Toll3 and Toll4 play a large role in Toll-pathway-dependent immune reactions, whereas spz7 plays a small part. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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12 pages, 8350 KiB

Open AccessArticle

Expression of Antimicrobic Peptide Piscidin1 in Gills Mast Cells of Giant Mudskipper Periophthalmodon schlosseri (Pallas, 1770)

by Alessio Alesci, Gioele Capillo, Doaa M. Mokhtar, Angelo Fumia, Roberta D’Angelo, Patrizia Lo Cascio, Marco Albano, Maria Cristina Guerrera, Ramy K. A. Sayed, Nunziacarla Spanò, Simona Pergolizzi and Eugenia Rita Lauriano

Int. J. Mol. Sci. 2022, 23(22), 13707; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213707 - 08 Nov 2022

Cited by 12 | Viewed by 1383

Abstract

The amphibious teleost Giant mudskipper (Periophthalmodon schlosseri, Pallas 1770) inhabit muddy plains and Asian mangrove forests. It spends more than 90% of its life outside of the water, using its skin, gills, and buccal-pharyngeal cavity mucosa to breathe in oxygen from the surrounding air. All vertebrates have been found to have mast cells (MCs), which are part of the innate immune system. These cells are mostly found in the mucous membranes of the organs that come in contact with the outside environment. According to their morphology, MCs have distinctive cytoplasmic granules that are released during the degranulation process. Additionally, these cells have antimicrobial peptides (AMPs) that fight a variety of infections. Piscidins, hepcidins, defensins, cathelicidins, and histonic peptides are examples of fish AMPs. Confocal microscopy was used in this study to assess Piscidin1 expression in Giant Mudskipper branchial MCs. Our results demonstrated the presence of MCs in the gills is highly positive for Piscidin1. Additionally, colocalized MCs labeled with TLR2/5-HT and Piscidin1/5-HT supported our data. The expression of Piscidin1 in giant mudskipper MCs highlights the involvement of this peptide in the orchestration of teleost immunity, advancing the knowledge of the defense system of this fish. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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15 pages, 940 KiB

Open AccessArticle

Identification of the Gene Repertoire of the IMD Pathway and Expression of Antimicrobial Peptide Genes in Several Tissues and Hemolymph of the Cockroach Blattella germanica

by Leo Zuber, Rebeca Domínguez-Santos, Carlos García-Ferris and Francisco J. Silva

Int. J. Mol. Sci. 2022, 23(15), 8444; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158444 - 30 Jul 2022

Cited by 3 | Viewed by 1676

Abstract

Antimicrobial peptide (AMP) genes, triggered by Toll and IMD pathways, are essential components of the innate immune system in the German cockroach Blattella germanica. Besides their role in killing pathogenic bacteria, AMPs could be involved in controlling its symbiotic systems (endosymbiont and microbiota). We found that the IMD pathway was active in the adult female transcriptomes of six tissues (salivary glands, foregut, midgut, hindgut, Malpighian tubules and fat body) and hemolymph. Total expression of AMP genes was high in hemolymph and salivary glands and much lower in the other sample types. The expression of specific AMP genes was very heterogeneous among sample types. Two genes, defensin_g10 and drosomycin_g5, displayed relevant expression in the seven sample types, although higher in hemolymph. Other genes only displayed high expression in one tissue. Almost no expression of attacin-like and blattellicin genes was observed in any sample type, although some of them were among the genes with the highest expression in adult female whole bodies. The expression of AMP genes in salivary glands could help control pathogens ingested with food and even determine gut microbiota composition. The low expression levels in midgut and hindgut are probably related to the presence of beneficial microbiota. Furthermore, a reduction in the expression of AMP genes in fat body could be the way to prevent damage to the population of the endosymbiont Blattabacterium cuenoti within bacteriocytes. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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20 pages, 10076 KiB

Open AccessArticle

Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison

by Daniel Conde, Pablo F. Garrido, Martín Calvelo, Ángel Piñeiro and Rebeca Garcia-Fandino

Int. J. Mol. Sci. 2022, 23(6), 3158; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063158 - 15 Mar 2022

Cited by 1 | Viewed by 2873

Abstract

Self-assembled cyclic peptide nanotubes with alternating D- and L-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antimicrobial peptides. Molecular dynamics simulations can be used to characterize these systems with atomic resolution at different time scales, providing information that is difficult to obtain via wet lab experiments. However, the performance of classical force fields typically employed in the simulation of biomolecules has not yet been extensively tested with this kind of highly constrained peptide. Four different classical force fields (AMBER, CHARMM, OPLS, and GROMOS), using a nanotube formed by eight D,L-α-cyclic peptides inserted into a lipid bilayer as a model system, were employed here to fill this gap. Significant differences in the pseudo-cylindrical cavities formed by the nanotubes were observed, the most important being the diameter of the nanopores, the number and location of confined water molecules, and the density distribution of the solvent molecules. Furthermore, several modifications were performed on GROMOS54a7, aiming to explore acceleration strategies of the MD simulations. The hydrogen mass repartitioning (HMR) and hydrogen isotope exchange (HIE) methods were tested to slow down the fastest degrees of freedom. These approaches allowed a significant increase in the time step employed in the equation of the motion integration algorithm, from 2 fs up to 5–7 fs, with no serious changes in the structural and dynamical properties of the nanopores. Subtle differences with respect to the simulations with the unmodified force fields were observed in the concerted movements of the cyclic peptides, as well as in the lifetime of several H-bonds. All together, these results are expected to contribute to better understanding of the behavior of self-assembled cyclic peptide nanotubes, as well as to support the methods tested to speed up general MD simulations; additionally, they do provide a number of quantitative descriptors that are expected to be used as a reference to design new experiments intended to validate and complement computational studies of antimicrobial cyclic peptides. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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17 pages, 2287 KiB

Open AccessArticle

Severe Natural Outbreak of Cryptocaryon irritans in Gilthead Seabream Produces Leukocyte Mobilization and Innate Immunity at the Gill Tissue

by Laura Cervera, Carmen González-Fernández, Marta Arizcun, Alberto Cuesta and Elena Chaves-Pozo

Int. J. Mol. Sci. 2022, 23(2), 937; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020937 - 15 Jan 2022

Cited by 15 | Viewed by 2229

Abstract

The protozoan parasite Cryptocaryon irritans causes marine white spot disease in a wide range of fish hosts, including gilthead seabream, a very sensitive species with great economic importance in the Mediterranean area. Thus, we aimed to evaluate the immunity of gilthead seabream after a severe natural outbreak of C. irritans. Morphological alterations and immune cell appearance in the gills were studied by light microscopy and immunohistochemical staining. The expression of several immune-related genes in the gills and head kidney were studied by qPCR, including inflammatory and immune cell markers, antimicrobial peptides (AMP), and cell-mediated cytotoxicity (CMC) molecules. Serum humoral innate immune activities were also assayed. Fish mortality reached 100% 8 days after the appearance of the C. irritans episode. Gill filaments were engrossed and packed without any space between filaments and included parasites and large numbers of undifferentiated and immune cells, namely acidophilic granulocytes. Our data suggest leukocyte mobilization from the head kidney, while the gills show the up-regulated transcription of inflammatory, AMPs, and CMC-related molecules. Meanwhile, only serum bactericidal activity was increased upon infection. A potent local innate immune response in the gills, probably orchestrated by AMPs and CMC, is triggered by a severe natural outbreak of C. irritans. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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Review

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28 pages, 1934 KiB

Open AccessReview

Unraveling the Role of Antimicrobial Peptides in Insects

by Sylwia Stączek, Małgorzata Cytryńska and Agnieszka Zdybicka-Barabas

Int. J. Mol. Sci. 2023, 24(6), 5753; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065753 - 17 Mar 2023

Cited by 18 | Viewed by 4512

Abstract

Antimicrobial peptides (AMPs) are short, mainly positively charged, amphipathic molecules. AMPs are important effectors of the immune response in insects with a broad spectrum of antibacterial, antifungal, and antiparasitic activity. In addition to these well-known roles, AMPs exhibit many other, often unobvious, functions in the host. They support insects in the elimination of viral infections. AMPs participate in the regulation of brain-controlled processes, e.g., sleep and non-associative learning. By influencing neuronal health, communication, and activity, they can affect the functioning of the insect nervous system. Expansion of the AMP repertoire and loss of their specificity is connected with the aging process and lifespan of insects. Moreover, AMPs take part in maintaining gut homeostasis, regulating the number of endosymbionts as well as reducing the number of foreign microbiota. In turn, the presence of AMPs in insect venom prevents the spread of infection in social insects, where the prey may be a source of pathogens. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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20 pages, 1299 KiB

Open AccessReview

Antigen Presentation and Autophagy in Teleost Adaptive Immunity

by Carolina Johnstone and Elena Chaves-Pozo

Int. J. Mol. Sci. 2022, 23(9), 4899; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094899 - 28 Apr 2022

Cited by 10 | Viewed by 2918

Abstract

Infectious diseases are a burden for aquaculture. Antigen processing and presentation (APP) to the immune effector cells that fight pathogens is key in the adaptive immune response. At the core of the adaptive immunity that appeared in lower vertebrates during evolution are the variable genes encoding the major histocompatibility complex (MHC). MHC class I molecules mainly present peptides processed in the cytosol by the proteasome and transported to the cell surface of all cells through secretory compartments. Professional antigen-presenting cells (pAPC) also express MHC class II molecules, which normally present peptides processed from exogenous antigens through lysosomal pathways. Autophagy is an intracellular self-degradation process that is conserved in all eukaryotes and is induced by starvation to contribute to cellular homeostasis. Self-digestion during autophagy mainly occurs by the fusion of autophagosomes, which engulf portions of cytosol and fuse with lysosomes (macroautophagy) or assisted by chaperones (chaperone-mediated autophagy, CMA) that deliver proteins to lysosomes. Thus, during self-degradation, antigens can be processed to be presented by the MHC to immune effector cells, thus, linking autophagy to APP. This review is focused on the essential components of the APP that are conserved in teleost fish and the increasing evidence related to the modulation of APP and autophagy during pathogen infection. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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16 pages, 2239 KiB

Open AccessReview

Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action

by Matthew Drayton, Julia P. Deisinger, Kevin C. Ludwig, Nigare Raheem, Anna Müller, Tanja Schneider and Suzana K. Straus

Int. J. Mol. Sci. 2021, 22(20), 11172; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011172 - 16 Oct 2021

Cited by 48 | Viewed by 4050

Abstract

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Immunology)

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