Current Pharmaceutical Biotechnology - Volume 16, Issue 2, 2015

Through many millennia of continuous evolution hosts and microorganisms have developed sophisticated and sometimes extremely complex mechanisms of coexisting through symbiosis and mutualism. It is now known that in humans, the population of commensal bacteria on or inside the body significantly outnumbers the host cells. Despite their numerical superiority, microorganisms have adjusted their physiological clocks to benefit themselves and at the same time their host through the maintenance of a healthy state. This very fine and multifaceted balance can be disrupted occasionally through the introduction of pathogens in the commensal bacterial population. The equilibrium is then perturbed to promote dysbiosis and the onset of disease. Through myriads of interactions within their host milieu, bacterial pathogens have developed mechanisms to sense bacterial or host-derived signalling molecules and adjust their physiology accordingly to favour their survival and propagation within their host. At the same time, the host has evolved systems to interfere with bacterial signalling in such a way as to support pathogen clearing and re-establishment of the balance. An example of a captivating interaction is the one involving the catecholamine hormones adrenaline and noradrenaline. This article will summarise the major findings involving host pathogen communication through bacterial or host-derived molecules and discuss ways to take advantage of our potential to interfere with this intricate signalling to profit the host and prolong a healthy life.

Firmly attached to different living or non-living, solid or fluid surfaces rich in nutrients and moisture, microbial biofilm is a matter of great interest due to its major importance for the healthcare community. Depending on common strategies such as mutual protection and hibernation (quiescent bacteria), the resistance, survival and virulence of microbial communities have large implications for human pathology, clinical environment and biomedical devices. The microbial biofilm is continuously changing, stimulating inflammation, increasing vascular permeability and preventing the action of macrophages. About 80% of human infections affecting the gastrointestinal, genitourinary and respiratory systems, oral mucosa and teeth, eyes, middle ear and skin are caused by biofilm-associated microorganisms. Therefore, the search for modern strategies is even more important as microbial biofilms resistant to conventional antibiotics, antiseptics and disinfectants are involved in the frequent treatment failures of some chronic inflammatory diseases and wounds. Natural products containing secondary metabolites, such as aromatic compounds, sulphurated derivatives, terpenoids (essential oils) and alkaloids as quorum-sensing inhibitors and biofilm disruptors, are promising alternatives for the prophylaxis and treatment of chronic infections. Surface modification of medical devices with non-polar functionalized nanoparticles stabilizes the natural compounds antibiofilm activity and inhibits microbial adhesion and biofilm formation and growth for a longer period of time. In this regard, an interdisciplinary approach is needed due to the large number of natural derivatives alone or in combination with biocompatible and biodegradable micro-/ nano-engineered materials.

This review highlights and discusses the impact of nanotechnology on the inhibition of microbial colonization and biofilm development on modified surface prosthetic devices. In the first part of the paper the current status of infections related to prosthetic devices and the inquiries resulting from the increased number of patients with these infections are briefly reviewed. Next we discuss several aspects about the implication of nanotechnology in prosthetic devices surface modification and its impact on the prevention of infections. The main aspects regarding the biocompatibility and the application of these nanomodified prosthetic devices in tissue engineering are also highlighted.

The development of effective packaging materials is crucial, because food microorganisms determine economic and public health issues. The current paper describes some of the most recent findings in regards of food preservation through novel packaging methods, using biodegradable polymers, efficient antimicrobial agents and nanocomposites with improved mechanical and oxidation stability, increased biodegradability and barrier effect comparatively with conventional polymeric matrices.

Owing to its physico-chemical characteristics, the biodegradable and biocompatible polymer derived from crustacean shells, Chitosan is one of the preferred candidates for green biomedical applications and also for several industries. Its solubility in acid solutions and ability to form complexes with anionic macromolecules to yield nanoparticles, microparticles and hydrogels, as well as the ability of chitosan based nanocomposites to remain stable at physiological pH recommend this polymer for the development of efficient drug delivery systems. This paper reviews the main utilities of chitosan as a drug delivery component and describes the most recent technologies which utilize this polymer for developing nanostructured systems with antimicrobial effect, offering a perspective of using these findings in new, ecological biomedical applications.

Plants are rich in a wide variety of secondary metabolites with antimicrobial properties. Phytochemistry studies on the plants extracts in general, and on essential oils (EOs) in particular are focused on the isolation and identification of the components of complex mixtures, in order to determine structure - activity correlations (i.e., physiological and/ or ecological roles, bases for the pharmacognosy studies). Problems as microbial resistance to existing antibiotics and the decline in the formulation of new antibiotics generated an increased interest in anti-infective herbal medicines. Some plants are known to be EOs producing, especialy superior plants, angiosperms and gymnosperms, belonging to approximately 50 families, most frequently Apiaceae, Lamiaceae, Myrtaceae, Pinaceae, Zingiberaceae, etc. The antimicrobial activity of EOs and of their components has been demonstrated on a variety of microorganisms. Our aim was to review relevant literature for identifying current research directions regarding EOs, in terms of antimicrobial effects, analysismethods and mechanisms of action. A plethora of methods have been used to test EOs antimicrobial properties concerning the microbial growth inhibition and/ or their anti-pathogenic effect. The reported methods contributed also to the elucidation of their mechanisms of action. Future research is needed for developing EOs related strategies in overlapping the multi-drug resistance and for reducing the required concentrations to achieve a particular antimicrobial and/ or antibiofilm effect to the human health benefit and/or for food safety purposes.

Antibiotic resistance is a major problem in current contemporary medicine and it has become a major concern of the 21st century. New resistance mechanisms developed by microorganisms spread greatly, threatening the ability to treat numerous infectious diseases, and increasing the number of nosocomial infections. Besides the role in immunology and glycobiology where they are used as hemaglutinine and identification of complex carbohydrates and glycoconjugates, lectins proved to mediate diversified biological functions like cytotoxicity, complement activation, cell-to-cell and host-pathogen communications, innate immune response, and cell-to-cell signalling. Recently, great interest has been developed for the research and applications of lectins in agriculture and medicine due to their antiparasitic and antimicrobial potentials. This review focuses on the recent data regarding the antimicrobial and antiparasitic activities of lectins, by presenting the role of lectins in host-pathogen interaction and also the cytotoxic effects on microorganisms and parasites. Identification and characterisation of new lectins with antimicrobial activity could serve as a natural alternative for the treatment of infections caused by antibiotic-resistant microorganisms and parasites.

L-asparaginase is an effective anti-neoplastic agent used in chemotherapy of acute lymphoblastic leukemia. One hundred and thirty actinomycete isolates were isolated from several soil samples collected from different localities in Egypt. All these isolates were purified and evaluated for their ability to produce L-asparaginase activity. Among them, strain NEAE-95 was selected and identified as Streptomyces parvus strain NEAE-95 based on morphological, cultural, physiological characteristics and 16S rRNA sequence. The sequence was deposited in the NCBI GenBank database under accession number KJ200341. L-asparaginase production by Streptomyces parvus NEAE-95 was optimized in shake flask culture. The Plackett–Burman statistical design was used for initial screening of sixteen factors for their significance on L-asparaginase production. Among the variables screened, incubation time, L-asparagine and yeast extract had significant effects on L-asparaginase production. The levels of these significant variables and their interaction effects were optimized by Box–Behnken statistical design. As a result, the maximal L-asparaginase production was achieved at the following fermentation conditions: g/L (dextrose 2, starch 20, L-asparagine 14, KNO3 2, yeast extract 2, K2HPO4 2, MgSO4.7H2O 0.1, NaCl 0.1, FeSO4.7H2O 0.01), pH 7, temperature 30°C, agitation speed 200 rpm, inoculum size 2%, v/v and incubation time 8 days.

Basidiocarps of Pleurotus ostreatus and Agrocybe cylindracea are characterized by high nutritional value and numerous medicinal activities, though bioactivities of their mycelia have not been sufficiently studied. The aim of the study was to evaluate antioxidant and antifungal potentials of P. ostreatus and A. cylindracea basidiocarp extracts, as well as those obtained from mycelia cultivated in common synthetic medium and media enriched with various agro-industrial residues. The free radical scavenging activity of the extracts was determined spectrophotometrically, based on DPPH• reduction while antifungal potential was studied by a microdilution method. The highest level of DPPH• scavenging ability was obtained by an extract of P. ostreatus mycelium cultivated in wheat bran-enriched medium, while control medium favoured the antioxidant potential of A. cylindracea mycelium. Phenol compounds were the main carriers of antioxidant activity that was demonstrated by high coefficients for correlations between total phenol contents in extracts and level of DPPH• scavenging (0.94 for P. ostreatus extracts and 0.91 for A. cylindracea extracts). Only the extracts of A. cylindracea basidiocarp and control mycelium, at a concentration of 1.33 mg/mL, inhibited the growth of Microsporum gypseum and Aspergillus flavus, while basidiocarp extract at 1.67 mg/mL also had fungicidal effect against M. gypseum. These results revealed a considerable antioxidant potential of submergedly-cultivated mycelium which showed higher antioxidant activity than basidiocarp extracts. This is very important because significant amounts of mycelium biomass could be obtained more easily, cheaper and in a more controllable way than basidiocarps cultivation.

In this study, sustained-release of GnRH antagonist peptide LXT-101 was realized through oil formulation, and their releasing characteristics in vitro and in vivo were investigated. In this formulation, the static interaction between cationic charged peptide LXT-101 and the negative charged phospholipid led to the formation of the phospholipid-peptide complex, by which LXT-101 was completely dissolved in oils. This formulation was prepared by mixing an aqueous solution of LXT-101 and empty SUV (small unilamellar liposomes) containing EPC (phosphatidylcholine) and DPPG (1, 2-dipalmitog-sn-glycero-3- phosphoglycerol) at an appropriate ratio, the mixture was subsequently lyophilized, and the resultant was dissolved in the oil to form a clear oily solution containing solubilized peptide LXT-101. With atomic force microscopy combined with Langmuir–Blodgett technology, the morphology of the particles in the oily solution were examined to be oval-shaped and the mean particle size was 150 nm in diameter. In pure water at 37°C, about 70~90 % of LXT-101 was released slowly from the oily formulation over 7 days. An effective sustained suppression of testosterone in beagle dogs could be achieved over a period of seven days with this LXT-101 oily formulation, by i.m. at a dose of 0.2 mg/kg (2 mg/ml). This formulation dramatically improved the bioactivity of LXT-101 compared to its aqueous solution. It was also found that when the concentration of peptide LXT-101 was up to or over 10 mg/ml in aqueous solution, there was no significant difference between the oily formulation and aqueous solution. This fact meant that LXT-101 itself could conduct sustained release in vivo by self-assembly of nanofibers.