Microbicidal Activity Research Articles

Engineering and characterization of human \u03b2-defensin-3 and its analogues and microcin J25 peptides against Mannheimia haemolytica and bovine neutrophils

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 in vitro against M. haemolytica. Three C-terminal analogues of HBD3 with all cysteines replaced with valines were manually synthesized using solid phase peptide synthesis. Since AMPs can act as chemoattractant we tested the chemotactic effect of HBD3, 28AA, 20AA, and 10AA peptides on bovine neutrophils in Boyden chamber. Minimum bactericidal concentration (MBC) assay showed that M. haemolytica was intermediately sensitive to HBD3, 28AA and 20AA analogues with an MBC of 50 µg/mL. The 10AA analogue had MBC 6.3 µg/mL which is likely a result of lower final inoculum size. MccJ25 didn’t have significant bactericidal effect below an MBC < 100 µg/mL. Bovine neutrophils showed chemotaxis towards HBD3 and 20AA peptides (P < 0.05) but not towards 28AA analogue. Co-incubation of neutrophils with any of the peptides did not affect their chemotaxis towards N-formyl-l-methionyl-l-leucyl-phenylalanine (fMLP). The data show that these peptides are effective against M. haemolytica and are chemotactic for neutrophils in vitro.

Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox).

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives with MI-Crobicidal and Antibiofilm Activity Enhanced by Combination with Iron Oxide Nanoparticles.

Antimicrobial resistance is one of the major public health threats at the global level, urging the search for new antimicrobial molecules. The fluorene nucleus is a component of different bioactive compounds, exhibiting diverse pharmacological actions. The present work describes the synthesis, chemical structure elucidation, and bioactivity of new O-aryl-carbamoyl-oxymino-fluorene derivatives and the contribution of iron oxide nanoparticles to enhance the desired biological activity. The antimicrobial activity assessed against three bacterial and fungal strains, in suspension and biofilm growth state, using a quantitative assay, revealed that the nature of substituents on the aryl moiety are determinant for both the spectrum and intensity of the inhibitory effect. The electron-withdrawing inductive effect of chlorine atoms enhanced the activity against planktonic and adhered Staphylococcus aureus, while the +I effect of the methyl group enhanced the anti-fungal activity against Candida albicans strain. The magnetite nanoparticles have substantially improved the antimicrobial activity of the new compounds against planktonic microorganisms. The obtained compounds, as well as the magnetic core@shell nanostructures loaded with these compounds have a promising potential for the development of novel antimicrobial strategies.

Ionic liquid mediated green synthesis of Ag-Au/Y2O3 nanoparticles using leaves extracts of Justicia adhatoda: Structural characterization and its biological applications

In the present work, a facile synthesis was applied for the silver-gold decorated yttrium oxide nanoparticles with the use of Justicia adhatoda (leaves extract) and [BMIM] PF6 (Ionic liquid) as a capping/stabilizing agent. The XRD analysis showed that Ag-Au/Y2O3 nanoparticles have a face-center cubic structure and crystallite size of 30 nm. The Y-O stretching bands were observed in the FT-IR spectrum at 464 to 495 cm−1. The band gap of the silver-gold decorated Y2O3 nanoparticles was estimated as 5.75 eV from the UV-DRS spectrum. In the SEM and TEM images, the morphology of silver-gold/Y2O3 nanoparticles shows a nanoflake-like structure. The presence of silver, gold, yttrium and oxygen of elements has been confirmed by the EDX spectrum. The antibacterial activity of the nanoparticles was evaluated for the Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria. The anticancer activity was also studied by the human cervical cancer cell line. The silver-gold decorated yttrium oxide nanoparticles revealed an exceptional microbicidal and antitumor activity when compared with yttrium oxide, silver decorated yttrium oxide and gold decorated yttrium oxide.

Hybrid Cyclobutane/Proline-Containing Peptidomimetics: The Conformational Constraint Influences Their Cell-Penetration Ability.

A new family of hybrid β,γ-peptidomimetics consisting of a repetitive unit formed by a chiral cyclobutane-containing trans-β-amino acid plus a Nα-functionalized trans-γ-amino-l-proline joined in alternation were synthesized and evaluated as cell penetrating peptides (CPP). They lack toxicity on the human tumoral cell line HeLa, with an almost negligible cell uptake. The dodecapeptide showed a substantial microbicidal activity on Leishmania parasites at 50 µM but with a modest intracellular accumulation. Their previously published γ,γ-homologues, with a cyclobutane γ-amino acid, showed a well-defined secondary structure with an average inter-guanidinium distance of 8–10 Å, a higher leishmanicidal activity as well as a significant intracellular accumulation. The presence of a very rigid cyclobutane β-amino acid in the peptide backbone precludes the acquisition of a defined conformation suitable for their cell uptake ability. Our results unveiled the preorganized charge-display as a relevant parameter, additional to the separation among the charged groups as previously described. The data herein reinforce the relevance of these descriptors in the design of CPPs with improved properties.

Chemical Composition and Antimicrobial Activities of Essential Oil from the Leaves of Acalypha wilkesiana on Pathogenic Microorganisms

Acalypha wilkesiana is a tropical plant used to treat a wide range of medical conditions. The leaves of A. wilkesiana were tested for phytochemicals with microbicide activity against a variety of microorganisms known to cause severe human infections. Antimicrobial efficacy of essential oil extracts from pulverised dried leaves of A. wilkesiana was examined. Phytochemical and proximate assessments of the leaves were carried out using standard techniques. The essential oil was extracted using hydro-distillation and collected using two processes. The first form was extraction for four hours straight, and the second mode involve hourly collection for four times. A total of five fractions of the essential oil were extracted. The chemical constituent of the oil was separated with Gas chromatography–mass spectrometry (GC-MS) in accordance with standard procedures. The proximate composition of leaves showed low moisture and high carbohydrate (61.39%). Tannins, flavonoids, and alkaloids were among the secondary metabolites found in the leaves. Six bioactive compounds including n-Hexadecanoic acid and 6-Benzamido-4-benzoyl-1, 2, 4-triazine-3, 5 were identified in the GC–MS analysis. The oils from A. wilkesiana leaves have excellent broad-spectrum antimicrobial activity at various concentrations on Staphylococcus species, Bacillus coagulans, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium and Candida albicans. It could not, however, inhibit the growth of Pseudomonas aeruginosa and Gardnerella vaginalis. The findings justify the usage of A. wilkesiana leaves in ethnomedicine for possible management of skin conditions, gastrointestinal problems as well as other related microbial infections.

S05.3: Potential use of antimicrobial peptide LL‐37 as a vaginal multipurpose prevention technology (MPT) reagent with spermicidal and microbicidal activity

S05.3: Potential use of antimicrobial peptide LL‐37 as a vaginal multipurpose prevention technology (MPT) reagent with spermicidal and microbicidal activity

Cytotoxicity and Microbicidal Activity of Commonly Used Organic Solvents: A Comparative Study and Application to a Standardized Extract from Vaccinium macrocarpon.

The cytotoxicity and microbicidal capacity of seven organic solvents commonly applied for studying plant extracts and bioactive compounds were systematically investigated based on international standards. Four cell lines of normal (CCL-1, HaCaT) or tumor (A-375, A-431) tissue origin, seven bacterial and one fungal strain were used. The impact of the least toxic solvents in the determination of in vitro cytotoxicity was evaluated using a standardized extract from Vaccinium macrocarpon containing 54.2% v/v proanthocyanidins (CystiCran®). The solvents ethanol, methoxyethanol and polyethylene glycol were the least cytotoxic to all cell lines, with a maximum tolerated concentration (MTC) between 1 and 2% v/v. Ethanol, methanol and polyethylene glycol were mostly suitable for antimicrobial susceptibility testing, with minimum inhibitory concentrations (MICs) ≥ 25% v/v. The MTC values of the solvents dimethyl sulfoxide, dimethoxyethane and dimethylformamide varied from 0.03% to 1.09% v/v. The MICs of dimethyl sulfoxide, methoxyethanol and dimethoxyethane were in the range of 3.125–25% v/v. The cytotoxic effects of CystiCran® on eukaryotic cell lines were directly proportional to the superimposed effect of the solvents used. The results of this study can be useful for selecting the appropriate solvents for in vitro estimation of the cytotoxic and growth inhibitory effects of bioactive molecules in eukaryotic and prokaryotic cells.

Radiation-induced synthesis of copper sulfide nanotubes with improved catalytic and antibacterial activities.

In the current paper, copper sulfide nanotubes have been successfully synthesized via the green, simple, and effective gamma-radiolysis method without adding any capping or reducing agents. The structural and morphological characteristics of the as-prepared CuS nanotubes were investigated by X-ray diffraction (XRD), N2 adsorption-desorption measurements at 77K, transmission electron microscopy (TEM), and ultraviolet-visible (UV-vis) spectroscopy, which all demonstrated the formation of pure CuS covellite phase with tubular morphology. The synthesized CuS nanotubes possessed not only high activity towards the reduction of both cationic (methylene blue) and anionic (Congo red) dyes in the presence of NaBH4 but also exhibited excellent reusability. In addition, the pseudo-first-order kinetic model represented the reduction of MB very well, and the value of the normalized rate constant (2.4 × 10-2s-1mg-1) was higher than those of other solid catalysts reported in the literature. Ultimately, CuS nanotubes were found to have a broad-spectrum microbicidal action against the common microbiota, such as Gram-positive (exemplified by Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (exemplified by Pseudomonas aeruginosa and Escherichia coli), yeast (exemplified by Candida albicans), and plant pathogenic fungi (exemplified by Aspergillus niger).

ДИФФЕРЕНЦИРОВАННАЯ ТРАНСФОРМАЦИЯ ФЕНОТИПА СУБПОПУЛЯЦИЙ НЕЙТРОФИЛЬНЫХ ГРАНУЛОЦИТОВ ПРИ ВИРУСНО-ВИРУСНЫХ И ГНОЙНЫХ БАКТЕРИАЛЬНЫХ ИНФЕКЦИЯХ У ИММУНОКОМПРОМЕТИРОВАННЫХ ДЕТЕЙ

Children with clinical signs of immunocompromise have impaired functioning of the immune system. At the same time, the state of subpopulations of multifunctional neutrophil granulocytes (NG), which provide antiviral and antibacterial protection, in such patients has been poorly studied. Objective of the study: to assess the features of the transformation of the phenotype of the three most significant subpopulations of NG, their association with impaired phagocytic and microbicidal activity in immunocompromised children with atypical viral-viral co-infections and bacterial infections, and to clarify their differential diagnostic significance. Materials and methods of research: the phenotypes of NG subpopulations expressing CD64, CD32, CD16, CD11b receptors, phagocytic and microbicidal activity of NG were studied in the peripheral blood of 43 immunocompromised children of both sexes aged of 5–9 years old suffering from recurrent ARVI, atypical chronic mono – or mixed herpes virus infections (HVI) and purulent bacterial infection. 3 study groups were formed: 1st – repeated ARVI/HVI mono, 2nd – repeated ARVI/HVI mixed, 3rd – minor purulent infection (MPI) and a comparison group (20 apparently healthy children). Results: different differentiated transformation of the phenotype of functionally significant subpopulations of NG associated with impaired functional activity of NG as well as with the incidence of viral co-infections (repeated ARVI and recurrent HVI mixed) and the severity of clinical manifestations of MPI has been identified in the studied groups. Conclusion. Еvaluation of the features of transformation of phenotype of NG subpopulations, their effector functions in immunocompromised children with atypical viral-viral co-infections and purulent bacterial infections, will allow in the future to optimize the methods of target immunotherapy aimed at remodulating the negatively transformed phenotype of NG subpopulations, correcting their dysfunctions and, thereby, significantly increase the clinical effectiveness of therapeutic and preventive measures.

Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

Production of bioactive selenium enriched crude exopolysaccharides via selenourea and sodium selenite bioconversion using Trametes versicolor

During a bioconversion to crude exopolysaccharides enriched with selenium from selenourea (SU-cEPS) and sodium selenite (SE-cEPS) in Trametes versicolor submerged culture, high selenium accumulation was achieved. The FTIR analysis detected two major fractions of selenium-cEPS samples: polysaccharides and proteins, indicating their proteoglycan character. Higher carbohydrate (595.98 ± 35.35 mg/g) and β-glucan (31.12 ± 1.76 mg/g) content of SE-cEPS compared to the SU-cEPS was established. Due to the partial dissolution of selenium-cEPS, the antibacterial and antioxidative potential of their soluble fractions (selenium-cEPSsol) were studied. Results indicated that selenium incorporation from different sources into mushroom's exopolysaccharides affected their biological activities. Analysis revealed that all tested Gram-positive and Gram-negative bacterial strains were susceptible to selenium-cEPSsol, with more pronounced microbicidal activity of SE-cEPSsol against Gram-positive bacteria. Although no differences between samples were observed regarding activity on Gram-negative bacteria, selenium incorporation into exopolysaccharides influenced their antibacterial activity against two Escherichia coli species. The HPLC amino acid analysis showed cationic character of selenium-cEPS protein fraction, indicating its potential participation in antimicrobial activities. Selenium-cEPSsol showed significant capacity to reduce the DPPH free radicals and a high ability to chelate Fe2+ ions as a consequence of its ligand characteristic and capability to coordinate with metal ions. Presence of D-rhamnose was confirmed in SE-cEPS, and it has contributed to its higher chelating ability compared to the SU-cEPSsol. The partial dissolution feature of selenium-cEPS samples, as well as established biological activities of the selenium-cEPSsol can be further investigated and applied in the food industry for elimination causatives of the oxidative stress and food-related pathogens.

Features of the immune status in chronic hepatitis C in patients with lymphopriliferative diseases

Tumor transformation of immunocompetent cells in patients with chronic lymphoproliferative diseases (CLPD) leads to the formation of secondary immune deficiency, which increases the prevalence of infectious complications. Whether the presence of hepatitis C virus (HCV) and the formation of chronic hepatitis (HCV) further weaken the immunoreactivity of the patient, remains poorly understood. The purpose of this work was to reveal the patterns of HCG formation in patients with CLPD with a detailed analysis of immune disorders associated with the chronicity of viral hepatitis C. Another aim of the study was to disclose the patterns of HCG formation in patients with CLP with a detailed analysis of immune disorders associated with the chronicity of viral hepatitis C. The comparative assessment of immunological and biochemical parameters was carried out in 110 patients with HCV (85 – chronic lymphocytic leukemia, 25 – non- Hodgkin lymphoma), with the presence of hepatitis C virus markers (n=20) and 90 patients negative for HCV. To identify intergroup differences, the method of nonparametric statistics was used: the Mann-Whitney criterion. Results. It was found that the group of HCV-infected patients is represented by younger persons compared to uninfected patients (median age – 44 years vs. 60 years, p=0.004). Analyzing the state of the immune system, we have revealed that regardless of the presence of chronic hepatitis C, all patients had a defect in both cellular and humoral immunity. The degree of immune deficiency did not have a direct dependence on viral liver damage. Moreover, in the presence of HCV infection, there was an increase in the microbicidal activity of neutrophils, as well as an increase in the expression of CD95+ on lymphoid cells. Cytokine levels during HCV contamination fluctuated in different directions. There was an increase in the level of ALT in the group of patients with HCV. Findings. The formation of immune deficiency in patients with CLPD is largely associated with the presence of oncopathology and practically does not depend on the presence of chronic hepatitis C.

ANTIMICROBIAL EFFECT OF IODOFORM AND CHLORHEXIDINE ON MUSEUM STRAINS OF MICROORGANISMS

Surgical tooth extraction can result in a number of complications. Alveolitis is an infectious and inflammatory process in the walls of a tooth socket that may occur after tooth extraction during at the oral surgery outpatient appointment. This condition is characterized by a partial or complete absence of a blood clot, called as "dry socket", and pain syndrome. There are various factors, which can contribute to the development of this process, but the most common are traumatic and infectious ones. For the local treatment of alveolitis, a number of drugs are used to eliminate inflammatory manifestations and pain syndrome. During an outpatient appointment for the treatment of alveolitis, antiseptic drugs as iodoform and chlorhexidine are most often used. Iodoform is an antiseptic widely used locally in oral surgery and in endodontics. Chlorhexidine is also widely used in dentistry as an antiseptic. The aim of this in vitro study is to investigate the antimicrobial properties of iodoform and chlorhexidine using museum strains of microorganisms. Materials and methods. Museum strains of Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 14990, Enterococcus faecalis ATCC 29212, Esherichia coli ATCC 25922, Candida albicans ATCC 10231 were used the studied cultures of microorganisms. The antimicrobial effect of iodoform and chlorhexidine was determined by a quantitative method of serial dilutions in broth and agar. For this purpose, we used iodoform suspension, which corresponded to 200.0 mg / ml of the working concentration of the agent. A 0.05% solution of chlorhexidine bigluconate was used that corresponded to 500 μg / ml of the working concentration of the agent. Results and discussion. Iodoform as powder in the studied concentrations caused an insignificant static effect on museum strains of E. faecalis, E. coli, but did not exhibit a bactericidal effect against them. In relation to the C. albicans strain, iodoform demonstrated fungiostatic properties. The S. epidermidis and S. aureus strains were resistant to iodoform. Chlorhexidine caused both inhibitory and microbicidal action on all studied strains of microorganisms.

Contribution of Essential Oils to the Fight against Microbial Biofilms—A Review

The increasing clinical use of artificial medical devices raises the issue of microbial contamination, which is a risk factor for the occurrence of biofilm-associated infections. A huge amount of scientific data highlights the promising potential of essential oils (EOs) to be used for the development of novel antibiofilm strategies. We aimed to review the relevant literature indexed in PubMed and Embase and to identify the recent directions in the field of EOs, as a new modality to eradicate microbial biofilms. We paid special attention to studies that explain the mechanisms of the microbicidal and antibiofilm activity of EOs, as well as their synergism with other antimicrobials. The EOs are difficult to test for their antimicrobial activity due to lipophilicity and volatility, so we have presented recent methods that facilitate these tests. There are presented the applications of EOs in chronic wounds and biofilm-mediated infection treatment, in the food industry and as air disinfectants. This analysis concludes that EOs are a source of antimicrobial agents that should not be neglected and that will probably provide new anti-infective therapeutic agents.

Mutagenicity of silver nanoparticles evaluated using whole-genome sequencing in mouse lymphoma cells

The increasing medical and food applications of silver nanoparticles (AgNPs) raise concerns about their safety, including the potential health consequences of human exposure. Previous studies found that AgNPs were negative in the Ames test due to both their microbicidal activity and the inability of nanoparticles to penetrate bacterial cell walls. Thus, the mutagenicity of AgNPs is still not completely clear, though they do induce chromosome damage, as suggested by many previous genotoxicity studies. In this study, whole-genome sequencing (WGS) was used to analyze the mutagenicity of AgNPs in mouse lymphoma cells expanded from single-cell clones. The cells were treated with AgNPs, 4-nitroquinolone-1-oxide (4-NQO) as the positive control, and vehicle controls. Both AgNPs and 4-NQO significantly increased mutation frequencies over their concurrent controls by 1.12-fold and 4.89-fold with mutation rates at 4-fold and 130-fold, respectively. AgNP-induced mutations mainly occurred at G:C sites with G:C > T:A transversions, G:C > A:T transitions, and deletions as the most commonly observed mutations. AgNPs also induced higher fold changes in tandem mutations. The results suggest that the WGS mutation assay conducted here can detect the low-level mutagenicity of AgNPs, providing substantial support for the use of the WGS method as a possible alternative assay with respect to the mutagenic assessment of nanomaterials.

In vitro phenotypic re-orientation of functionally important neutrophil subpopulations and their microbicidal activity in the children with purulent inflammatory diseases influenced by glucosaminil muramildipeptide

Numerous studies over last decade have shown that functional capacity of neutrophil granulocytes (NG) determines the course and outcome of many diseases. Identification of phenotypic variants of functionally significant NG subpopulations is a new approach allows us to assess the adequacy or deficiency of NG involvement into infectious inflammation processes at molecular level. An opportunity of reorienting a deficient NG subpopulational phenotype in purulent inflammatory diseases due to the rearrangement of the receptor set induced by various immunotropic substances may serve as a key to recovery of normal NG functioning. Our aim was to study the effect of glucosaminylmuramyldipeptide (GMDP) under in vitro conditions upon the phenotypic profile of four functionally significant subpopulations, i.e., CD62L + CD63 - NG, CD62L + CD63 + NG and CD64 - CD32 + CD16 + CD11b + NG, CD64 + CD32 + CD16 + CD11b + NG, along with assessment of expression density of appropriate membrane molecules and NG microbicidal activity in the children with purulent inflammatory diseases. 90 samples of peripheral blood (PC) were taken from children 2 to 4 years old, including 12 children with minor purulent infection (MPI), and 7 children were studied as conditionally healthy controls. Their peripheral blood was incubated for 60 minutes at 37 °C with GMP (10 -6 g/l). Using flow cytometry technique, the relative numbers of some NG subpopulations, i.e., CD64 - CD16 + CD32 + CD11b + NG, CD64 + CD16 + CD32 + CD11b + NG, CD62L + CD63 - NG, CD62L + CD63 + NG were evaluated, and the phenotype features of each subpopulation were investigated according to the density of appropriate membrane molecule expression (MFI). In parallel, phagocytic and microbicidal activity of NG was tested in these study groups. The obtained data indicate for presence of for distinct NG subpopulations, both in healthy children and in children with MPI. We have revealed phenotypic transformation of the four studied NG subpopulations from MPI patients including disturbed phagocytic and microbicidal functions of the cells. Using of this in vitro system, we have shown that the transformed phenotype of the four functionally significant NG subpopulations of MPI patients was re-arranged under GMDP treatment. At the same time, the number of CD62L + CD63 + NG and CD64 - CD32 + CD16 + CD11b + NG subpopulations was increased, along with decreased amounts of CD64 + CD32 + CD16 + CD11b + NG and CD62L + CD63 - NG subpopulations, being accompanied by restoration of microbicidal activity of NGs. The obtained data allow us to accomplish current understanding of immunotropic effects of GMDP, and to extend the potential scope of its experimental and clinical application. The new data on GMDP effects revealed by in vitro system, i.e. phenotype rearrangement of functionally significant NG subpopulations CD64 - CD16 + CD32 + CD11b + , CD64 + CD16 + CD32 + CD11b + , CD62L + CD63 - , CD62L + CD63 + in atypical purulent inflammatory diseases in children, may be used in the future in order to develop innovative strategies of immunotherapy aiming for correction of NG dysfunction in children with MPI.

Non-neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice.

Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T‐ and B‐cell responses. The administration of virus‐specific non‐neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV‐specific nnAbs bind preferentially Ly6Chi inflammatory monocytes (IMs), promote their infection in an Fc‐receptor independent way, and support acquisition of APC properties. By constituting additional T‐cell priming opportunities, IMs promote early activation of virus‐specific CD8 T cells, eventually tipping the balance between T‐cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T‐cell exhaustion and an Fc‐receptor independent protective mechanism provided by LCMV‐specific nnAbs against the establishment of chronic infection.

Core-shell chitosan/PVA-based nanofibrous scaffolds loaded with Satureja mutica or Oliveria decumbens essential oils as enhanced antimicrobial wound dressing

Wounds are prone to bacterial infections, which cause a delayed healing process. Regarding the emergence of bacterial resistance to common antibiotics, using natural antimicrobial agents can be beneficial. Chitosan is a biological polymer, which has shown partial antioxidant and antimicrobial activities. In this study, core-shell nanofibrous scaffolds composed of chitosan (CS)/polyvinyl alcohol (PVA) as the core and polyvinylpyrrolidone (PVP)/ maltodextrin (MD) as the shell were developed. Satureja mutica (S. mutica) or Oliveria decumbens (O. decumbens) essential oil (EO) was encapsulated into the core of the produced scaffolds. The broth microdilution analysis showed significant antimicrobial activity of the EOs. The SEM analysis indicated that the unloaded and loaded core-shell scaffolds with S. mutica or O. decumbens EO had a uniform, beadless structure with fiber mean diameters of 210 ± 50, 250 ± 45, and 225 ± 46 nm, respectively. The CS/PVA-PVP/MD and CS/PVA/EO-PVP/MD scaffolds indicated suitable mechanical properties. The addition of the studied EOs enhanced the antioxidant activity of the scaffolds. The antimicrobial test of produced scaffolds showed that loading of 10% S. mutica or O. decumbens EO could broaden the microbicidal activity of the CS/PVA-PVP/MD scaffolds. These results revealed that the CS/PVA/EO-PVP/MD nanofibrous scaffolds are promising candidates for wound dressing.

Physicochemical properties and antimicrobial activity of nanocomposite films based on carboxymethylcellulose and silver nanoparticles

AbstractSilver nanoparticles (AgNPs) stabilized by sodium carboxymethylcellulose (Na‐CMC) with degree of substitution (DS) 0.65‐0.90 and degree of polymerization (DP) 200‐600 were synthesized by photochemical method. The structural, physico‐chemical, and physico‐mechanical properties as well as antimicrobial activity of polymer films containing the Na‐CMC and AgNPs were studied. The shape, quantity, and size of the AgNPs embedded into the Na‐CMC films were determined by UV‐Vis spectroscopy, ZETASIZER Nano ZS, atomic force microscopy and transmission electron microscopy. It was found that the increase of silver nitrate concentration in solution of Na‐CMC followed by photoirradiation leads to the change of size and shape of AgNPs. The AgNPs in the range of size from 5 to 35 nm were found to enhance the microbicidal activities of the Na‐CMC films.