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’.

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 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

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.

scholarly journals Molecular characterization of a novel β-defensin isoform from the red-toothed trigger fish, Odonus niger (Ruppel, 1836)

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
S. Neelima ◽  
K. Archana ◽  
P. P. Athira ◽  
M. V. Anju ◽  
V. V. Anooja ◽  
...  
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Disulfide Bonds ◽  
Signal Sequence ◽  
Phylogenetic Analyses ◽  
Functional Characterization ◽  
Innate Immune ◽  
Mature Peptide

Abstract Background The concern regarding a post-antibiotic era with increasing drug resistance by pathogens imposes the need to discover alternatives for existing antibiotics. Antimicrobial peptides (AMPs) with their versatile therapeutic properties are a group of promising molecules with curative potentials. These evolutionarily conserved molecules play important roles in the innate immune system of several organisms. The β-defensins are a group of cysteine rich cationic antimicrobial peptides that play an important role in the innate immune system by their antimicrobial activity against the invading pathogens. The present study deals with a novel β-defensin isoform from the red-toothed trigger fish, Odonus niger. Total RNA was isolated from the gills, cDNA was synthesized and the β-defensin isoform obtained by polymerase chain reaction was cloned and subjected to structural and functional characterization in silico. Results A β-defensin isoform could be detected from the gill mRNA of red-toothed trigger fish, Odonus niger. The cDNA encoded a 63 amino acid peptide, β-defensin, with a 20 amino acid signal sequence followed by 43 amino acid cationic mature peptide (On-Def) having a molecular weight of 5.214 kDa and theoretical pI of 8.89. On-Def possessed six highly conserved cysteine residues forming disulfide bonds between C1–C5, C2–C4, and C3–C6, typical of β-defensins. An anionic pro-region was observed prior to the β-defensin domain within the mature peptide. Clustal alignment and phylogenetic analyses revealed On-Def as a group 2 β-defensin. Furthermore, it shared some structural similarities and functional motifs with β-defensins from other organisms. On-Def was predicted to be non-hemolytic with anti-bacterial, anti-viral, anti-fungal, anti-cancer, and immunomodulatory potential. Conclusion On-Def is the first report of a β-defensin from the red-toothed trigger fish, Odonus niger. The antimicrobial profile showed the potential for further studies as a suitable candidate for antimicrobial peptide therapeutics.

Antimicrobial Peptides of Marine Crustaceans: The Potential and Challenges of Developing Therapeutic Agents

2018 ◽  
Vol 25 (19) ◽  
pp. 2245-2259 ◽  
Author(s):  
Negar T. Zanjani ◽  
Monica Miranda-Saksena ◽  
Anthony L. Cunningham ◽  
Fariba Dehghani
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Antimicrobial Agents ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Innate Immune ◽  
Genetic Composition ◽  
Structure Activity ◽  
Marine Crustaceans

The alarming increase of antimicrobial resistance has led to a growing number of studies aiming to develop novel antimicrobial therapeutics. Natural antimicrobial peptides possess a potent and broad-spectrum antimicrobial activity combined with diverse and unique structural motifs, which confer their different mechanisms of action. These peptides are ubiquitous in organisms and are integral to the innate immune system. Recently, identification of antimicrobial peptides from marine crustaceans has become the centre of attention of many researchers. This increasing interest stems from the remarkable diversity in the structural and genetic composition of these peptides compared to terrestrial counterparts. Thus, peptides from marine crustaceans can serve as future templates for novel antimicrobial agents. Here, we provide an overview of various antimicrobial peptides from the marine crustaceans, their antimicrobial activity and structure- activity relationships. We also discuss the potential and challenges of their development as new antimicrobial agents.

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 Defining principles that influence antimicrobial peptide activity against capsulatedKlebsiella pneumoniae

2020 ◽  
Vol 117 (44) ◽  
pp. 27620-27626 ◽  
Author(s):  
Renee M. Fleeman ◽  
Luis A. Macias ◽  
Jennifer S. Brodbelt ◽  
Bryan W. Davies
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Extracellular Polysaccharide ◽  
Innate Immune ◽  
Potential Mechanism ◽  
Active Peptide ◽  
Peptide Analog ◽  
Physical Interactions ◽  
Strong Antimicrobial Activity

The extracellular polysaccharide capsule ofKlebsiella pneumoniaeresists penetration by antimicrobials and protects the bacteria from the innate immune system. Host antimicrobial peptides are inactivated by the capsule as it impedes their penetration to the bacterial membrane. While the capsule sequesters most peptides, a few antimicrobial peptides have been identified that retain activity against encapsulatedK. pneumoniae,suggesting that this bacterial defense can be overcome. However, it is unclear what factors allow peptides to avoid capsule inhibition. To address this, we created a peptide analog with strong antimicrobial activity toward severalK. pneumoniaestrains from a previously inactive peptide. We characterized the effects of these two peptides onK. pneumoniae, along with their physical interactions withK. pneumoniaecapsule. Both peptides disrupted bacterial cell membranes, but only the active peptide displayed this activity against capsulatedK. pneumoniae. Unexpectedly, the active peptide showed no decrease in capsule binding, but did lose secondary structure in a capsule-dependent fashion compared with the inactive parent peptide. We found that these characteristics are associated with capsule-peptide aggregation, leading to disruption of theK. pneumoniaecapsule. Our findings reveal a potential mechanism for disrupting the protective barrier thatK. pneumoniaeuses to avoid the immune system and last-resort antibiotics.

scholarly journals Cryptococcus neoformans Cells in Biofilms Are Less Susceptible than Planktonic Cells to Antimicrobial Molecules Produced by the Innate Immune System

2006 ◽  
Vol 74 (11) ◽  
pp. 6118-6123 ◽  
Author(s):  
Luis R. Martinez ◽  
Arturo Casadevall
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Cryptococcus Neoformans ◽  
Innate Immune System ◽  
Capsular Polysaccharide ◽  
Pathogenic Fungus ◽  
Innate Immune ◽  
Planktonic Cells ◽  
Phagocytic Cells ◽  
Immune Effector

ABSTRACT The human pathogenic fungus Cryptococcus neoformans can form biofilms on polystyrene plates and medical devices in a process that requires capsular polysaccharide release. Although biofilms are known to be less susceptible to antimicrobial drugs, little is known about their susceptibility to antimicrobial molecules produced by the innate immune system. In this study, we investigated the susceptibility of C. neoformans cells in biofilm and planktonic states to oxidative and nonoxidative antimicrobial molecules produced by phagocytic cells. The effects of various immune effector molecules on the fungal mass, metabolic activity, and architecture of C. neoformans biofilms were measured by colony counts, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide reduction, and confocal microscopy, respectively. Biofilms were more resistant than planktonic cells to oxidative stress but remained vulnerable to cationic antimicrobial peptides. However, melanized biofilms were significantly less susceptible to antimicrobial peptides than nonmelanized biofilms. These results suggest that the biofilm phenotype increases resistance against host immune mechanisms, a phenomenon that could contribute to the ability of biofilm-forming microbes to establish persistent infections.

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