A Peptide Found in Human Serum, Derived from the C-Terminus of Albumin, Shows Antifungal Activity In Vitro and In Vivo.

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597-609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources.

Efficacy of N-acetylcysteine, D-mannose and Morinda citrifolia to Treat Recurrent Cystitis in Breast Cancer Survivals.

BACKGROUND/AIM: Breast cancer survivors in adjuvant therapy, frequently experience the estrogen deficiency with genitourinary symptoms mostly represented by recurrent bacterial cystitis. The objective of the present study was to evaluate the effectiveness of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract (NDM), when associated to antibiotic therapy, in reducing the persistence of recurrent cystitis in this risk population. PATIENTS AND METHODS: Sixty breast cancer survived women with recurrent cystitis were retrospectively examined. Group 1, comprised of 40 patients treated with antibiotic therapy associated with NDM lasting for six months, Group 2 comprised of 20 patients treated with antibiotics alone. RESULTS: The use of NDM in combination with antibiotic therapy showed a significant reduction in positive urine cultures, compared to antibiotics alone. Subjects of Group 1 rather than those of Group 2, showed improvement in symptoms score of urgency, frequency, urge incontinence, recurrent cystitis, bladder and urethral pain. CONCLUSION: In breast cancer survived women affected by genitourinary discomfort, the combination of NDM and antibiotic therapy showed a greater efficacy in reducing urinary tract infections and urinary discomfort with respect to antibiotic use only.

Prospective study to compare antibiosis versus the association of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing urinary tract infections in patients submitted to urodynamic investigation.

BACKGROUND: The abuse of antimicrobical drugs has increased the resistance of microorganisms to treatments, thus to make urinary tract infections (UTIs) more difficult to eradicate. Among natural substances used to prevent UTI, literature has provided preliminary data of the beneficial effects of D-mannose, N-acetylcysteine, and Morinda citrifolia fruit extract, due to their complementary mechanism of action which contributes respectively to limit bacteria adhesion to the urothelium, to destroy bacterial pathogenic biofilm, and to the anti-inflammatory and analgesic activity. The purpose of this study was to compare the administration of an association of D-mannose, N-acetylcysteine (NAC) and Morinda citrifolia extract versus antibiotic therapy in the prophylaxis of UTIs potentially associated with urological mini-invasive diagnostics procedures, in clinical model of the urodynamic investigation. METHODS: 80 patients eligible for urodynamic examination, 42 men and 38 women, have been prospectively enrolled in the study and randomised in two groups (A and B) of 40 individuals. Patients of group A followed antibiotic therapy with Prulifloxacine, by mouth 400 mg/day for 5 days, while patients of the group B followed the association of mannose and NAC therapy, two vials/day for 7 days. Ten days after the urodynamic study, the patients were submitted to urine examination and urine culture. RESULTS: The follow up assessment didn't show statistical significant difference between the two groups regarding the incidence of UTI. CONCLUSIONS: The association of mannose and NAC therapy resulted similar to the antibiotic therapy in preventing UTIs in patients submitted to urodynamic examination. This result leads to consider the possible use of these nutraceutical agents as a good alternative in the prophylaxis of the UTI afterwards urological procedures in urodynamics.

A Naturally Occurring Antibody Fragment Neutralizes Infectivity of Diverse Infectious Agents.

A phosphorylated peptide, named K40H, derived from the constant region of IgMs was detected in human serum by liquid chromatography coupled to high-resolution mass spectrometry. Synthetic K40H proved to exert a potent in vitro activity against fungal pathogens, and to inhibit HIV-1 replication in vitro and ex vivo. It also showed a therapeutic effect against an experimental infection by Candida albicans in the invertebrate model Galleria mellonella. K40H represents the proof of concept of the innate role that naturally occurring antibody fragments may exert against infectious agents, shedding a new light upon the posthumous role of antibodies and opening a new scenario on the multifaceted functionality of humoral immunity.

Imogolite: an aluminosilicate nanotube endowed with low cytotoxicity and genotoxicity.

High-aspect-ratio nanomaterials (HARN) (typically, single-walled carbon nanotubes (SWCNT) or multiwalled carbon nanotubes (MWCNT)) impair airway barrier function and are toxic to macrophages. Here, we assess the biological effects of nanotubes of imogolite (INT), a hydrated alumino-silicate [(OH)3Al2O3SiOH] occurring as single-walled NT, on murine macrophages and human airway epithelial cells. Cell viability was assessed with resazurin. RT-PCR was used to study the expression of Nos2 and Arg1, markers of classical or alternative macrophage activation, respectively, and nitrite concentration in the medium was determined to assess NO production. Epithelial barrier integrity was evaluated from the trans-epithelial electrical resistance (TEER). Potential genotoxicity of INT was assessed with comet and cytokinesis-block micronucleus cytome assays. Compared to MWCNT and SWCNT, INT caused much smaller effects on RAW264.7 and MH-S macrophage viability. The incubation of macrophages with INT at doses as high as 120 µg/cm(2) for 72 h did not alter either Nos2 or Arg1 expression nor did it increase NO production, whereas IL6 was induced in RAW264.7 cells but not in MH-S cells. INT did not show any genotoxic effect in RAW264.7 and A549 cells except for a decrease in DNA integrity observed in epithelial A549 cells after treatment with the highest dose (80 µg/cm(2)). No significant change in permeability was recorded in Calu-3 epithelial cell monolayers exposed to INT, whereas comparable doses of both SWCNT and MWCNT lowered TEER. Thus, in spite of their fibrous nature, INT appear not to be markedly toxic for in vitro models of lung-blood barrier cells.

Antimicrobial activity of poultry bone and meat trimmings hydrolyzates in low-sodium turkey food.

This research was aimed at the evaluation of the antimicrobial activity exerted by poultry protein hydrolyzates derived from industrial leftovers added to minced turkey meat, intended for the production of burgers for human consumption. Hydrolyzates were obtained through enzymatic hydrolysis from poultry bone and meat trimmings, as by-products from the poultry industry. Colony forming unit assays, under both laboratory and industrial conditions, were performed to assess microbial growth. Poultry protein hydrolyzates inhibited microbial growth occurring in semi-finished turkey meat during the normal retention period because of their water holding capacity resulting in a decreased water activity. Overall, the findings demonstrated that poultry protein hydrolyzates could decrease mesophilic, psychrophilic, and thermophilic bacterial growth for the entire product shelf-life. Bacterial growth inhibition obtained in minced turkey meat by addition of poultry protein hydrolyzates (1.5%), hygroscopic amino acids mixture (1.5%) or sodium chloride (1%) was similar. It is suggested that the use of hydrolyzates could allow the reduction of salt content in poultry meat based products leading to the production of low-sodium turkey food still maintaining acceptable sensory characteristics.

Antibody Peptide based antifungal immunotherapy.

Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast killer phenomenon to the production of Ab-derived peptides characterized by in vitro and in vivo fungicidal activity will be focused. In particular, Abs that mimic the antimicrobial activity of a killer toxin ("antibiobodies") and antifungal peptides derived from antibiobodies (killer peptide) and other unrelated Abs [complementarity determining regions (CDR)-based and constant region (Fc)-based synthetic peptides] are described. Mycological implications in terms of reevaluation of the yeast killer phenomenon, roles of antibiobodies in antifungal immunity, of ß-glucans as antifungal targets and vaccines, and of Abs as sources of an unlimited number of sequences potentially active as new immunotherapeutic tools against fungal agents and related mycoses, are discussed.

Peptides of the constant region of antibodies display fungicidal activity.

Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents.

Killer peptide: a novel paradigm of antimicrobial, antiviral and immunomodulatory auto-delivering drugs.

The incidence of life-threatening viral and microbial infections has dramatically increased over recent decades. Despite significant developments in anti-infective chemotherapy, many issues have increasingly narrowed the therapeutic options, making it imperative to discover new effective molecules. Among them, small peptides are arousing great interest. This review will focus in particular on a killer peptide, engineered from an anti-idiotypic recombinant antibody that mimics the activity of a wide-spectrum antimicrobial yeast killer toxin targeting ß-glucan cell-wall receptors. The in vitro and in vivo antimicrobial, antiviral and immunomodulatory activities of killer peptide and its ability to spontaneously and reversibly self-assemble and slowly release its active dimeric form over time will be discussed as a novel paradigm of targeted auto-delivering drugs.