Andrea Fulgione

New perspectives for natural antimicrobial peptides: application as antinflammatory drugs in a murine model

BackgroundAntimicrobial peptides (AMPs) are an ancient group of defense molecules. AMPs are widely distributed in nature (being present in mammals, birds, amphibians, insects, plants, and microorganisms). They display bactericidal as well as immunomodulatory properties. The aim of this study was to investigate the antimicrobial and anti-inflammatory activities of a combination of two AMPs (temporin B and the royal jellein I) against Staphylococcus epidermidis.ResultsThe temporin B (TB-KK) and the royal jelleins I, II, III chemically modified at the C terminal (RJI-C, RJII-C, RJIII-C), were tested for their activity against 10 different Staphylococcus epidermidis strains, alone and in combination. Of the three royal jelleins, RJI-C showed the highest activity. Moreover, the combination of RJI-C and TB-KK (MIX) displayed synergistic activity. In vitro, the MIX displayed low hemolytic activity, no NO2- production and the ability to curb the synthesis of the pro-inflammatory cytokines TNF-α and IFN-γ to the same extent as acetylsalicylic acid. In vivo, the MIX sterilized mice infected with Staphylococcus epidermidis in eleven days and inhibited the expression of genes encoding the prostaglandin-endoperoxide synthase 2 (COX-2) and CD64, two important parameters of inflammation.ConclusionThe study shows that the MIX – a combination of two naturally occurring peptides - displays both antimicrobial and anti-inflammatory activities.

A novel synthetic peptide from a tomato defensin exhibits antibacterial activities against Helicobacter pylori

Defensins are a class of cysteine‐rich proteins, which exert broad spectrum antimicrobial activity. In this work, we used a bioinformatic approach to identify putative defensins in the tomato genome. Fifteen proteins had a mature peptide that includes the well‐conserved tetradisulfide array. We selected a representative member of the tomato defensin family; we chemically synthesized its γ‐motif and tested its antimicrobial activity. Here, we demonstrate that the synthetic peptide exhibits potent antibacterial activity against Gram‐positive bacteria, such as Staphylococcus aureus A170, Staphylococcus epidermidis, and Listeria monocytogenes, and Gram‐negative bacteria, including Salmonella enterica serovar Paratyphi, Escherichia coli, and Helicobacter pylori. In addition, the synthetic peptide shows minimal (<5%) hemolytic activity and absence of cytotoxic effects against THP‐1 cells. Finally, SolyC exerts an anti‐inflammatory activity in vitro, as it downregulates the level of the proinflammatory cytokines TNF‐α and IFN‐γ. Copyright

Antimicrobial peptides from plants: stabilization of the γ core of a tomato defensin by intramolecular disulfide bond

Cysteine‐containing antimicrobial peptides of diverse phylogeny share a common structural signature, the γ core, characterized by a strong polarization of charges in two antiparallel β sheets. In this work, we analyzed peptides derived from the tomato defensin SolyC07g007760 corresponding to the protein γ core and demonstrated that cyclization of the peptides, which results in segregation of positive charges to the turn region, produces peptides very active against Gram negative bacteria, such as Salmonella enterica and Helicobacter pylori. Interestingly, these peptides show very low hemolytic activity and thus represent a scaffold for the design of new antimicrobial peptides. Copyright

Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications.

Epistatic interaction between MyD88 and TIRAP against Helicobacter pylori.

The genes MyD88 and TIRAP encode the adaptor proteins MyD88 and TIRAP. TIRAP plays the crucial role of activating the MyD88‐dependent pathway, which in turn controls the immune response (innate and adaptive) to Helicobacter pylori. We looked for an association of MyD88 and TIRAP with H. pylori infection. Cases and controls were genotyped at the polymorphic sites MyD88 rs6853 and TIRAP rs8177374 by real‐time PCR. When the genes were analyzed separately, only TIRAP was associated with infection. When the genes were analyzed concurrently, certain combinations of MyD88 and TIRAP protected the host against H. pylori colonization more efficiently than could be done by TIRAP alone.

Structural data and immunomodulatory properties of a water-soluble heteroglycan extracted from the mycelium of an Italian isolate of Ganoderma lucidum

Abstract Mushrooms produce a wide range of bioactive polysaccharides, different from each other in chemical structure and biological effects. In the last years, the idea to develop functional foods or drugs containing fungal polysaccharides is attracting great attention. Fruiting bodies of Basidiomycetes Ganoderma lucidum are commonly used in Oriental medicine to treat several disorders. G. lucidum polysaccharides – mainly β-glucans and heteroglycans – have numerous biological properties such as antitumour and immunomodulatory activities. This report shows, by gene expression analyses and bioenergetic assays, immunomodulatory properties and capacity to improve glucose metabolism of a water-soluble heteroglycan extracted from mycelium of an Italian isolate of G. lucidum. The findings suggest the use of the heteroglycan as probiotic or ingredient in functional foods, being easy to produce and disperse in a food matrix thanks to its water-solubility. Heteroglycan could exert protective effects in pro-inflammatory conditions and benefits for people characterised by suppressed immune response.

Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection

Background The resistance of Helicobacter pylori to the antibiotic therapy poses the problem to discover new therapeutic approaches. Recently it has been stated that antibacterial, immunomodulatory, and antioxidant properties of lactoferrin are increased when this protein is surface-linked to biomimetic hydroxyapatite nanocrystals. Objective Based on these knowledge, the aim of the study was to investigate the efficacy of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles with cell free supernatant from probiotic Lactobacillus paracasei as an alternative therapy against Helicobacter pylori infection. Methods Antibacterial and antinflammatory properties, humoral antibody induction, histopathological analysis and absence of side effects were evaluated in both in vitro and in vivo studies. Results The tests carried out have been demonstrated better performance of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles combined with cell free supernatant from probiotic Lactobacillus paracasei compared to both lactoferrin and probiotic alone or pooled. Conclusion These findings indicate the effectiveness and safety of our proposed therapy as alternative treatment for Helicobacter pylori infection.

QCM-based immunosensor for rapid detection of Salmonella Typhimurium in food

Salmonella Typhimurium is one of the main causes of outbreaks and sporadic cases of human gastroenteritis. At present, the rapid detection of this pathogen is a major goal of biosensing technology applied to food safety. In fact, ISO standardized culture method takes up to ten days to provide a reliable response. In this paper, we describe a relatively simple protocol for detecting Salmonella Typhimurium in chicken meat based on a Quartz-Crystal Microbalance (QCM), which leads to a limit of detection (LOD) less than of 10° CFU/mL and requires a pre-enrichment step lasting only 2 h at 37 °C. The reliability of the proposed immunosensor has been demonstrated through the validation of the experimental results with ISO standardized culture method. The cost-effectiveness of the procedure and the rapidity of the QCM-based biosensor in providing the qualitative response make the analytical method described here suitable for applications in food inspection laboratory and throughout the chain production of food industry.

Author Correction: The hypothesis that Helicobacter pylori predisposes to Alzheimer’s disease is biologically plausible

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.