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1.
ACS Chem Biol ; 17(7): 1824-1830, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35730734

ABSTRACT

Fungus-growing ants are defended by antibiotic-producing bacterial symbionts in the genus Pseudonocardia. Nutrients provisioned by the ants support these symbionts but also invite colonization and competition from other bacteria. As an arena for chemically mediated bacterial competition, this niche offers a window into ecological antibiotic function with well-defined competing organisms. From multiple colonies of the desert specialist ant Trachymyrmex smithi, we isolated Amycolatopsis bacteria that inhibit the growth of Pseudonocardia symbionts under laboratory conditions. Using bioassay-guided fractionation, we discovered a novel analog of the antibiotic nocamycin that is responsible for this antagonism. We identified the biosynthetic gene cluster for this antibiotic, which has a suite of oxidative enzymes consistent with this molecule's more extensive oxidative tailoring relative to similar tetramic acid antibiotics. High genetic similarity to globally distributed soil Amycolatopsis isolates suggest that this ant-derived Amycolatopsis strain may be an opportunistic soil strain whose antibiotic production allows for competition in this specialized niche. This nocamycin analog adds to the catalog of novel bioactive molecules isolated from bacterial associates of fungus-growing ants, and its activity against ant symbionts represents, to our knowledge, the first putative ecological function for the widely distributed enoyl tetramic acid family of antibiotics.


Subject(s)
Ants , Animals , Anti-Bacterial Agents/pharmacology , Ants/microbiology , Bacteria , Fungi , Polyketides , Soil , Symbiosis
2.
J Inorg Biochem ; 101(7): 1059-69, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17555823

ABSTRACT

Chromium (III) is an essential micronutrient required for normal protein, fat and carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein into muscle and convert sugar into energy. A broad spectrum of research investigations including in vitro, in vivo and clinical studies demonstrated the beneficial effects of novel oxygen- coordinated niacin-bound chromium (III) complex (NBC) in promoting glucose-insulin sensitivity, lipid profile, cardioprotective ability and lean body mass. This study examined the long-term safety of NBC by orally administering either 0 or 25 ppm or the human equivalency dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive weeks to male and female Sprague-Dawley rats. Animals of each group and each gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical and ocular health, feed and water intake, selected organ weights as such and as a percentage of liver and brain weight, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4% and 9.6% in female rats, respectively, in the NBC treatment groups. No significant changes were observed in hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluation between control and NBC groups at these time points. These findings, thus far, are in agreement with the subchronic studies in terms of the safety of NBC.


Subject(s)
Chromium Compounds/administration & dosage , Niacin/chemistry , Oxygen/chemistry , Administration, Oral , Animals , Body Weight/drug effects , Brain/drug effects , Brain/growth & development , Chromium Compounds/chemistry , Chromium Compounds/pharmacokinetics , DNA Fragmentation/drug effects , Eating/drug effects , Female , Humans , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/growth & development , Liver/metabolism , Male , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Therapeutic Equivalency , Time Factors
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