Proline-Rich Antimicrobial Peptides from Invertebrates.

Antimicrobial peptides (AMPs) constitute a large and diverse group of molecules with antibacterial, antifungal, antiviral, antiprotozoan, and anticancer activity. In animals, they are key components of innate immunity involved in fighting against various pathogens. Proline-rich (Pr) AMPs are characterized by a high content of proline (and arginine) residues that can be organized into Pro-Arg-Pro motifs.

Enhanced Antifungal Activity of Amphotericin B Bound to Albumin: A "Trojan Horse" Effect of the Protein.

Amphotericin B (AmB) is a life-saving and widely used antifungal antibiotic, but its therapeutic applicability is limited due to severe side effects. Here, we report that the formulation of the drug based on a complex with albumin (BSA) is highly effective against at relatively low concentrations, which implies lower toxicity to patients. This was also concluded based on the comparison with antifungal activities of other popular commercial formulations of the drug, such as Fungizone and AmBisome.

Unraveling the Role of Antimicrobial Peptides in Insects.

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.

Effect of amide protoporphyrin derivatives on immune response in Apis mellifera.

The intracellular microsporidian parasite Nosema ceranae is known to compromise bee health by induction of energetic stress and downregulation of the immune system. Porphyrins are candidate therapeutic agents for controlling Nosema infection without adverse effects on honeybees. In the present work, the impact of two protoporphyrin IX derivatives, i.

Synthesis and Study of Antifungal Properties of New Cationic Beta-Glucan Derivatives.

The interaction of positively charged polymers (polycations) with a biological membrane is considered to be the cause of the frequently observed toxicity of these macromolecules. If it is possible to obtain polymers with a predominantly negative effect on bacterial and fungal cells, such systems would have great potential in the treatment of infectious diseases, especially now when reports indicate the growing risk of fungal co-infections in COVID-19 patients. We describe in this article cationic derivatives of natural beta-glucan polymers obtained by reacting the polysaccharide isolated from (SB) and (CI) with glycidyl trimethyl ammonium chloride (GTMAC).

Fungal α-1,3-Glucan as a New Pathogen-Associated Molecular Pattern in the Insect Model Host .

Recognition of pathogen-associated molecular patterns (PAMPs) by appropriate pattern recognition receptors (PRRs) is a key step in activating the host immune response. The role of a fungal PAMP is attributed to β-1,3-glucan. The role of α-1,3-glucan, another fungal cell wall polysaccharide, in modulating the host immune response is not clear.

A comparison of the production of antimicrobial peptides and proteins by Galleria mellonella larvae in response to infection with two Pseudomonas aeruginosa strains differing in the profile of secreted proteases.

The work presents identification of antimicrobial peptides and proteins (AMPs) in the hemolymph of Galleria mellonella larvae infected with two Pseudomonas aeruginosa strains (ATCC 27,853 and PA18), differing in the profile of secreted proteases. The insects were immunized with bacteria cultivated in rich (LB) and minimal (M9) media, which resulted in appearance of a similar broad set of AMPs in the hemolymph. Among them, 13 peptides and proteins were identified, i.

Activation of cellular immune response in insect model host Galleria mellonella by fungal α-1,3-glucan.

Alpha-1,3-glucan, in addition to β-1,3-glucan, is an important polysaccharide component of fungal cell walls. It is reported for many fungal species, including human pathogenic genera: Aspergillus, Blastomyces, Coccidioides, Cryptococcus, Histoplasma and Pneumocystis, plant pathogens, e.g.

Choline Supplementation Sensitizes to Apolipophorin III.

The growth of can be inhibited by apolipophorin III (apoLp-III) which is an insect homologue of human apolipoprotein E., and choline-cultured cells are considerably more susceptible to apoLp-III than bacteria grown without choline supplementation. In the present study, the interactions of apoLp-III with intact cells cultured without and with exogenous choline were analyzed to explain the basis of this difference.

Identification and characterization of spp. and their susceptibility to insect apolipophorin III.

This study investigated the effect of an insect antimicrobial protein, apolipophorin III (apoLp-III), against two newly isolated, identified and characterized clinical strains of spp. Both strains were identified by 16S rRNA sequencing and metabolic and phenotypic profiling. The antibacterial activity of apoLp-III was tested using a colony counting assay.

Bioactivity studies of porphyrinoids against microsporidia isolated from honeybees.

Microsporidian infections are dangerous to honeybees due to the absence of an efficient treatment for nosemosis. In the present work, the abilities of several porphyrins to directly inactivate microsporidia derived from Nosema-infected honeybees were studied in vitro. Amide derivatives of protoporphyrin IX (PPIX) conjugated with one and two amino acid moieties were synthesized, and their activities were compared with those of two cationic porphyrins, TMePyP and TTMePP.

Proline-Rich Antimicrobial Peptides in Medicinal Maggots of Interact With Bacterial DnaK But Do Not Inhibit Protein Synthesis.

In the search for new antibiotics to combat multidrug-resistant microbes, insects offer a rich source of novel anti-infectives, including a remarkably diverse array of antimicrobial peptides (AMPs) with broad activity against a wide range of species. Larvae of the common green bottle fly are used for maggot debridement therapy, and their effectiveness in part reflects the large panel of AMPs they secrete into the wound. To investigate the activity of these peptides in more detail, we selected two structurally different proline rich peptides (Lser-PRP2 and Lser-PRP3) in addition to the α-helical peptide Lser-stomoxyn.

Insect Defense Proteins and Peptides.

The composition of insect hemolymph can change depending on many factors, e.g. access to nutrients, stress conditions, and current needs of the insect.

Antifungal Activity of Anionic Defense Peptides: Insight into the Action of Anionic Peptide 2.

Anionic antimicrobial peptides constitute an integral component of animal innate immunity, however the mechanisms of their antifungal activity are still poorly understood. The action of a unique anionic peptide 2 (AP2) against fungal pathogen was examined using different microscopic techniques and Fourier transform infrared (FTIR) spectroscopy. Although the exposure to AP2 decreased the survival rate of cells, the viability of protoplasts was not affected, suggesting an important role of the fungal cell wall in the peptide action.

Aspergillus niger α-1,3-glucan acts as a virulence factor by inhibiting the insect phenoloxidase system.

Phenoloxidase (PO) is a key enzyme in the melanization process involved in elimination of pathogens in insects. The PO system is rapidly activated in response to pathogen recognition. Inhibition of PO activity can be a way to avoid immune response and increase infection effectiveness.

The insect antimicrobial peptide cecropin A disrupts uropathogenic Escherichia coli biofilms.

Current antibiotics cannot eradicate uropathogenic Escherichia coli (UPEC) biofilms, leading to recurrent urinary tract infections. Here, we show that the insect antimicrobial peptide cecropin A (CecA) can destroy planktonic and sessile biofilm-forming UPEC cells, either alone or when combined with the antibiotic nalidixic acid (NAL), synergistically clearing infection in vivo without off-target cytotoxicity. The multi-target mechanism of action involves outer membrane permeabilization followed by biofilm disruption triggered by the inhibition of efflux pump activity and interactions with extracellular and intracellular nucleic acids.

Modes of the antibiotic activity of amphotericin B against Candida albicans.

Amphotericin B is an antibiotic used as the "gold standard" in the treatment of life-threatening fungal infections. Several molecular mechanisms have been proposed to explain exceptionally high effectiveness of amphotericin B in combating fungi. In the present work, we apply fluorescence lifetime imaging microscopy to track, step by step, modes of the toxic activity of amphotericin B towards a clinical strain of Candida albicans.

Pseudomonas aeruginosa alkaline protease exhibits a high renaturation capability.

Thermally induced unfolding and renaturation capability of alkaline proteases (AprA) of three Pseudomonas aeruginosa strains, i.e. ATCC 27853 and two clinical isolates, was examined.

Studies on the interactions of neutral Galleria mellonella cecropin D with living bacterial cells.

Cecropins constitute an important family of insect antimicrobial peptides involved in humoral innate immune response. In comparison with the highly basic cecropins A and B, cecropins D are less cationic and more hydrophobic. Interestingly, cecropins D were described only in lepidopteran insects, e.

[Different faces of phenoloxidase in animals].

Phenoloxidases are oxidoreducting enzymes whose main function is the oxidation of phenols. The term phenoloxidase is often used interchangeably to describe three different enzymes: tyrosinase (EC 1.14.

[Metalloproteases and their inhibitors: role in pathogenesis of selected examples].

Proteolytic enzymes and their inhibitors are crucial in host-pathogen interaction. Metalloproteases secreted by pathogenic microbes play an important role in destroying not only host tissues but also their immune proteins. Metalloproteinase inhibitors, in contrast, may serve as effective therapeutic agents, which is especially important because of the increasing number of microorganisms resistant to known antibiotics.

Studies on localization and protein ligands of Galleria mellonella apolipophorin III during immune response against different pathogens.

A lipid-binding protein apolipophorin III (apoLp-III), an exchangeable component of lipophorin particles, is involved in lipid transport and immune response in insects. In Galleria mellonella, apoLp-III binding to high-density lipophorins and formation of low-density lipophorin complexes upon immune challenge was reported. However, an unanswered question remains whether apoLp-III could form different complexes in a pathogen-dependent manner.

Galleria mellonella lysozyme induces apoptotic changes in Candida albicans cells.

The greater wax moth Galleria mellonella has been increasingly used as a model host to determine Candida albicans virulence and efficacy of antifungal treatment. The G. mellonella lysozyme, similarly to its human counterpart, is a member of the c-type family of lysozymes that exhibits antibacterial and antifungal activity.

The lipid composition of Legionella dumoffii membrane modulates the interaction with Galleria mellonella apolipophorin III.

Apolipophorin III (apoLp-III), an insect homologue of human apolipoprotein E (apoE), is a widely used model protein in studies on protein-lipid interactions, and anti-Legionella activity of Galleria mellonella apoLp-III has been documented. Interestingly, exogenous choline-cultured Legionella dumoffii cells are considerably more susceptible to apoLp-III than non-supplemented bacteria. In order to explain these differences, we performed, for the first time, a detailed analysis of L.

The functional interaction between abaecin and pore-forming peptides indicates a general mechanism of antibacterial potentiation.

Long-chain proline-rich antimicrobial peptides such as bumblebee abaecin show minimal activity against Gram-negative bacteria despite binding efficiently to specific intracellular targets. We recently reported that bumblebee abaecin interacts with Escherichia coli DnaK but shows negligible antibacterial activity unless it is combined with sublethal doses of the pore-forming peptide hymenoptaecin. These two bumblebee peptides are co-expressed in vivo in response to a bacterial challenge.