Tetramic acid based alkaloids from Aspergillus amoenus Roberg strain UP197-antibiotic properties and new pyranterreones

The fungus Aspergillus amoenus Roberg strain UP197 was shown to produce antibacterial tetramic acid based alkaloids. Two new compounds, pyranterreone I and J (1 and 2), were isolated and characterized, in addition to the known compounds cordylactam, 7-hydroxycordylactam, pyranterreone C, D, F and G. Neither the pyranterreones nor the cordylacctams had previously been tested for antimicrobial activity. Thus, all isolated compounds were tested against a panel of clinically important bacteria and fungi. Pyranterreone C was active against Gram-positive and Gram-negative bacteria, with minimal inhibitory concentrations (MIC) between 1 and 8 mu g/mL, whereas the MICs for all other compounds were >32 mu g/mL. Pyranoterreone C was cytotoxic towards HepG2 cells, and since pyranterreone C reacted rapidly with the nucleophile cysteine, it is likely that the observed antibacterial activity is due to the chemical reactivity rather than enzymatic affinity, making it unsuitable for development as an antibacterial drug

Treatment of Atopic Dermatitis with a Low-histamine Diet

Atopic dermatitis (AD) has numerous trigger factors. The question of whether foods can aggravate AD remains open to debate. Although a number of published papers have detailed the relationship between food allergies and AD, little research has examined the question of how food intolerance affects AD. For the purposes of this study, a six-year-old Korean boy with AD was admitted to the hospital for evaluation of the possibility of food, particularly pork, as a triggering factor in his skin disease. He had a history of worsening of symptoms when eating pork. Total serum IgE concentration was 157 IU/ml. House dust was class 2.2 (1.5 IU/ml) in MAST. All other MAST items were negative. In an oral food challenge test, he showed a positive result after eating 200 g of pork, but did not show a positive result after eating 60 g of pork. After discharge, we attempted to keep him on a balanced diet that included various types of food and prohibited him from eating food that contains a high level of histamine. After keeping the patient on a balanced and low-histamine dietary regimen, his AD symptoms showed improvement and have not worsened for more than seven months. A low-histamine, balanced diet could be helpful for AD patients having symptoms that resemble histamine intolerance in which their AD symptoms worsened after intake of histamine-rich foods, but in which food allergy tests are negative

Study on administration of 1,5-anhydro-D-fructose in C57BL/6J mice challenged with high-fat diet

1,5-Anhydro-D-fructose (AF) is a mono-saccharide directly formed from starch and glycogen by the action of α-1,4-glucan lyase (EC 4.2.2.13). Our previous study has indicated that AF increases glucose tolerance and insulin secretion in NMRI mice after administration through a gastric gavage in a single dose at 150 mg per mouse. In this study, we used high-fat feeding of C57BL/6J mice to examine the influence of long-term administration of AF on glucose-stimulated insulin secretion in vivo and in vitro. We found that 8-weeks of high-fat feeding increased body weight, fasting blood glucose and insulin levels in C57BL/6J mice when compared to mice fed normal diet. Impaired glucose tolerance was also observed in mice receiving 8-weeks of high-fat diet. In contrast, AF (1.5 g/kg/day), administered through drinking water for 8-weeks, did not affect body weight or food and water intake in mice fed either the high-fat or normal diet. There was no difference in basal blood glucose or insulin levels between AF-treated and control group. Oral glucose tolerance test (OGTT) showed that AF did not affect glucose-stimulated insulin secretion in mice. In in vitro studies with isolated islets, AF did not influence glucose-stimulated insulin secretion in mice receiving either high-fat or normal diet. We therefore conclude that when given through drinking water for 8 weeks at 1.5 g/kg/day, AF has no effect on glucose-stimulated insulin secretion in C57BL/6J mice challenged with a high-fat diet

Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway

Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A–C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 μM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 μM).Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases/[U54 AI57153]/GLRCE/Estados UnidosArmy Research Office/[W911NF-12-1-0059]/ARO/Estados UnidosNational Institutes of Health/[1R01GM098350]/NIH/Estados UnidosInternational Cooperative Biodiversity Groups-Fogarty International Center/[U01 TW007404]/ICBG/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA