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Antimicrobial mechanism of action of surfactant lipid preparations in enteric Gram-negative bacilli

JOURNAL OF APPLIED MICROBIOLOGY 2000年第3期89卷 397-403页

作者： Hamouda, T Baker, JR Univ Michigan Sch Med Dept Internal Med Div Allergy Ann Arbor MI 48109 USA Univ Michigan Sch Med Ctr Biol Nanotechnol Ann Arbor MI 48109 USA

Two surfactant lipid preparations (SLPs) were investigated to determine their mechanism of antimicrobial action. 8N8, a water-in-oil emulsion, and W60C, a liposome, both have bactericidal activity against Gram-positive bacteria and non-enteric Gram-negative bacteria. Additionally, W60C is bactericidal for enteric Gram-negative bacilli when suspended in deionized water. Zeta potential measurements suggested that the resistance of Gram-negative bacilli to 8N8 might be caused by ionic repulsion. Addition of 50 mu mol l(-1) ethylene diamine tetra acetic acid in 100 mmol l(-1) Tris buffer to either SLPs yielded efficient bactericidal activity against Gramnegative bacilli. This appeared to be due to disruption of the outer membrane and the chelation of divalent cations, as the addition of excess calcium inhibited the antimicrobial effect. Electron microscopy studies documented that 8N8 disrupts the bacterial cell wall, lysing the bacteria, while W60C fuses and internalizes within the cell, causing damage without immediate cell lysis. Understanding the mechanisms of action of these biocidal formulations will help to produce improved formulations with broader spectra of activity.

关键词：抗菌药/药理学细胞膜通透性/药物作用细胞壁/药物作用细胞壁/超微结构消毒药(剂)/药理学乳状剂/药理学大肠杆菌革兰氏阴性兼性厌氧杆菌/药物作用脂质体/药理学膜融合/药物作用显微镜检查电子表面活性剂/药理学

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Effect of cellular filamentation on adventurous and social gliding motility of Myxococcus xanthus

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1999年第26期96卷 15178-15183页

作者： Sun, H Yang, ZM Shi, WY Univ Calif Los Angeles Inst Mol Biol Los Angeles CA 90095 USA Univ Calif Los Angeles Sch Dent Los Angeles CA 90095 USA

Filamentous bacterial cells often provide biological information that is not readily evident in normal-size cells, In this study, the effect of cellular filamentation on gliding motility of Myxococcus xanthus, a Gram-negative social bacterium, was investigated. Elongation of the cell body had different effects on adventurous and social motility of M. xanthus. The rate of A-motility was insensitive to cell-body elongation whereas the rate of S-motility was reduced dramatically as the cell body got longer, indicating that these two motility systems work in different ways. The study also showed that filamentous wild-type cells glide smoothly with relatively straight, long cell bodies. However, filamentous cells of certain social motility mutants showed zigzag, tangled cell bodies on a solid surface, apparently a result of a lack of coordination between different fragments within the filaments. Further genetic and biochemical analyses indicated that the uncoordinated movements of these mutant filaments were correlated with the absence of cell surface fibril materials, indicating a possible new function for fibrils.

关键词：细胞壁/药物作用头孢氨苄/药理学行走/生理学黄色黏球菌/药物作用黄色黏球菌/生理学黄色黏球菌/超微结构

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Acceleration of hyaluronidase production in the course of batch cultivation of Clostridium perfringens can be achieved with bacteriolytic enzymes

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LETTERS IN APPLIED MICROBIOLOGY 2000年第3期30卷 203-206页

作者： Zukalte, V Biziulevicius, GA Inst Immunol Immunobiotechnol Sector LT-2021 Vilnius Lithuania

As Clostridium perfringens hyaluronidase has cell-bound enzyme features, an enzymatic approach has been designed to facilitate the release of hyaluronidase into culture through increasing the clostridial cell wall permeability. As a result of the application of lytic peptidase from Actinomyces rutgersenis, beta-N-acetylglucosaminidase and beta-N-acetylmuramidase (both from Bacillus subtilis) commercially available preparations at the end of the producer's exponential growth phase, a 5.3-, 4.8- and 4.0-fold acceleration, respectively (but no enhancement), of hyaluronidase production in the course of batch cultivation of Cl. perfringens has been achieved. This also resulted in an approximately 10-fold reduction in undesirable side lecithinase activity irrespective of the bacteriolytic enzyme preparation used.

关键词：乙酰氨基葡糖苷酶/药理学放线菌属/酶学枯草芽孢杆菌/酶学细胞壁/药物作用产气荚膜梭菌/酶学产气荚膜梭菌/生长和发育糖苷水解酶类/药理学透明质酸葡糖胺酶/代谢肽水解酶类/药理学通透性磷脂酶类/分析磷脂酶类/代谢时间因素

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INHIBITION OF BACTERIAL WALL LYSINS BY LIPOTEICHOIC ACIDS AND RELATED COMPOUNDS

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1975年第3期67卷 1128-1135页

作者： CLEVELAND, RF HOLTJE, JV WICKEN, AJ TOMASZ, A DANEOMOORE, L SHOCKMAN, GD TEMPLE UNIV SCH MEDDEPT MICROBIOL & IMMUNOLPHILADELPHIAPA 19122 ROCKEFELLER UNIV NEW YORKNY 10021

Lipoteichoic acid (LTA) from several Gram-positive microorganisms, Forssman antigen (Fag) from Diplococcus pneumoniae R36A, and an acidic lipopolysaccharide (ALP) from Micrococcus luteus were examined for effects on four wall lysis systems. The LTAs inhibited the N-acetylmuramidases of Streptococcus faecalis and Lactobacillus acidophilus , and the amidase of Bacillus subtilis 168. Deacylated LTA failed to inhibit. LTAs failed to inhibit the amidase of pneumococcus. Fag inhibited the pneumococcal amidase, but had no effect on the other three systems.

关键词：细菌/酶学细胞壁/药物作用细胞壁/酶学粪肠球菌/酶学 Forssman抗原水解酶类/拮抗剂和抑制剂动力学乳杆菌属/药物作用乳杆菌属/酶学嗜酸乳杆菌/酶学干酪乳杆菌/酶学脂多糖类/药理学链球菌属/药物作用链球菌属/酶学肺炎链球菌磷壁酸类/药理学

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Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第1期97卷 418-423页

作者： Harth, G Zamecnik, PC Tang, JY Tabatadze, D Horwitz, MA Univ Calif Los Angeles Div Infect Dis Dept Med Sch Med Los Angeles CA 90095 USA Massachusetts Gen Hosp Charlestown MA 02129 USA Hybridon Inc Milford MA 01757 USA

New antibiotics to combat the emerging pandemic of drug-resistant strains of Mycobacterium tuberculosis are urgently needed. We have investigated the effects on M. tuberculosis of phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of glutamine synthetase, an enzyme whose export is associated with pathogenicity and with the formation of a poly-L-glutamate/glutamine cell wall structure. Treatment of virulent M. tuberculosis with 10 mu M antisense PS-ODNs reduced glutamine synthetase activity and expression by 25-50% depending on whether one. two, or three different PS-ODNs were used and the PS-ODNs' specific target sites on the mRNA. Treatment with PS-ODNs of a recombinant strain of Mycobacterium smegmatis expressing M. tuberculosis glutamine synthetase selectively inhibited the recombinant enzyme but not the endogenous enzyme for which the mRNA transcript was mismatched by 2-4 nt, Treatment of M. tuberculosis with the antisense PS-ODNs also reduced the amount of poly-L-glutamate/glutamine in the cell wall by 24%. Finally, treatment with antisense PS-ODNs reduced M. tuberculosis growth by 0.7 logs (1 PS-ODN) to 1.25 logs (3 PS-ODNs) but had no effect on the growth of M, smegmatis, which does not export glutamine synthetase nor possess the poly-L-glutamate/glutamine (P-L-glx) cell wall structure. The experiments indicate that the antisense PS-ODNs enter the cytoplasm of M. tuberculosis and bind to their cognate targets. Although more potent ODN technology is needed, this study demonstrates the feasibility of using antisense ODNs in the antibiotic armamentarium against M. tuberculosis.

关键词：抗结核药/药理学抗结核药/治疗应用细胞分裂/药物作用细胞壁/药物作用 DNA 反义/药理学 DNA 反义/治疗应用酶抑制剂/药理学乙胺丁醇/药理学谷氨酰胺连接酶/拮抗剂和抑制剂谷氨酰胺连接酶/遗传学耻垢分枝杆菌/药物作用耻垢分枝杆菌/酶学结核分枝杆菌/酶学结核分枝杆菌/遗传学肽类/代谢肽聚糖/代谢聚谷氨酸/代谢 RNA 信使/药物作用

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INFLUENCE OF CONCANAVALIN-A ON AUTOLYSIS OF GAMETES FROM CHLAMYDOMONAS-REINHARDII

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ARCHIVES OF MICROBIOLOGY 1975年第3期103卷 225-230页

作者： CLAES, H MAX PLANCK INST BIOL ABT MELCHERSCORRENS STR 41D-7400 TUBINGENFED REP GER

The phytohemagglutinin concanavalin A inhibited zygote formation of Chlamydomonas reinhardii. 15--50 mug lectin/ml not only interfered with the mating reaction, but also with cell wall lysis of gametes and zoospores in a crude autolysin preparation gained from copulating gametes. Further, the structure of cell walls shed into the medium after autolysis in the course of the mating reaction and after lysis "from without" in the crude autolysin preparation was stabilized by Con A. Therefore, it must be assumed that the lectin inhibited zygote formation of C. reinhardii by interfering with autolysis of the cell walls of the gametes. Though Con A inhibited the lytic processes of C. reinhardii, an activation of the autolytic system in theta gametes by the lectin was found to compete with its inhibitory reaction. Con A induced autolysis of theta gametes was dependent on adherence of the cells by their flagella to the surface of the culture vessel or the liquid medium and did not occur in cultures stirred by rotation. The interferences of Con A with the autolytic serum of C. rienhardii were inhibited by methyl-alpha-D-mannopyrano-side and to a lesser degree by glucose, indicating that the carbohydrate binding sites of the lectin were involved in its reactions with the cells.

关键词：结合竞争性细胞壁/药物作用衣滴虫属/细胞学衣滴虫属/药物作用伴刀豆球蛋白A/药理学酶激活生殖细胞/药物作用己糖类/代谢甲基甘露糖苷类/代谢卵子发生/药物作用合子女(雌)性

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Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2000年第3期46卷 391-395页

作者： Bosne-David, S Barros, V Verde, SC Portugal, C David, HL Univ Nova Lisboa Inst Higiene & Med Trop Ctr Malaria & Outras Doencas Trop P-1200 Lisbon Portugal

Subinhibitory concentrations of bacitracin, vancomycin and other inhibitors of cell wall synthesis reversed to varying extents the intrinsic resistance of Mycobacterium tuberculosis to clarithromycin. Ethambutol reversed clarithromycin resistance in all of the M. tuberculosis strains studied regardless of their susceptibility to this drug.

关键词：抗菌药/药理学抗结核药/药理学细胞壁/药物作用细胞壁/代谢克拉霉素/药理学抗药性微生物药物协同作用乙胺丁醇/药理学微生物敏感性试验结核分枝杆菌/药物作用结核/微生物学人类

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Inhibitors of the fungal cell wall.: Synthesis of 4-aryl-4-N-arylamine-1-butenes and related compounds with inhibitory activities on β(1-3) glucan and chitin synthases

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BIOORGANIC & MEDICINAL CHEMISTRY 2000年第4期8卷 691-698页

作者： Urbina, JM Cortés, JCG Palma, A López, SN Zacchino, SA Enriz, RD Ribas, JC Kouznetzov, VV Univ Nacl Rosario Fac Ciencias Bioquim & Farmaceut RA-2000 Rosario Santa Fe Argentina Fac Quim Bioquim & Farm Chacabuco & Pedernera RA-5700 San Luis Argentina Ind Univ Santander Sch Chem Lab Fine Organ Chem Bucaramanga Colombia Inst Microbiol Bioquim Edificio Dept Salamanca 37007 Spain

As part of our project devoted to the search for antifungal agents, which act via a selective mode of action, we synthesized a series of new 4-aryl- or 4-alkyl-N-arylamine-1-butenes and transformed some of them into 2-substituted 4-methyl-tetrahydroquinolines and quinolines by using a novel three-step synthesis. Results obtained in agar dilution assays have shown that 4-aryl homoallylamines not possessing halogen in their structures, tetrahydroquinolines and quinolines, display a range of antifungal properties in particular against Epidermophyton floccosum and Microsporum canis. Regarding the mode of action, all active compounds showed in vitro inhibitory activities against beta(1-3) glucan-synthase and mainly against chitin-synthase. These enzymes catalyze the synthesis of beta(1-3) glucan and chitin, respectively, major polymers of the fungal cell wall. Since fungal but not mammalian cells are encased in a cell wall, its inhibition may represent a useful mode of action for these antifungal compounds. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：烯丙胺/类似物和衍生物烯丙胺/化学合成烯丙胺/化学烯丙胺/药理学抗真菌药/化学合成抗真菌药/化学抗真菌药/药理学细胞壁/药物作用细胞壁/酶学壳多糖合酶/拮抗剂和抑制剂酶抑制剂/化学合成酶抑制剂/化学酶抑制剂/药理学表皮癣菌属/药物作用表皮癣菌属/酶学糖原合成酶/拮抗剂和抑制剂微生物敏感性试验小孢子菌属/药物作用小孢子菌属/酶学光谱分析

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Inhibition of the establishment of zygotic polarity by protein tyrosine kinase inhibitors leads to an alteration of embryo pattern in Fucus

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DEVELOPMENTAL BIOLOGY 2000年第2期219卷 165-182页

作者： Corellou, F Potin, P Brownlee, C Kloareg, B Bouget, FY CNRS Biol Stn UMR 1931 F-29680 Roscoff France Labs Goemar Biol Stn UMR 1931 F-29680 Roscoff France Marine Biol Assoc United Kingdom Lab Plymouth PL1 2PB Devon England

Fucoid algae, including the genus Fucus and Pelvetia, are recognized as model systems to study early embryogenesis in plants. In particular the zygotes of these fucoid algae are highly suitable experimental systems for investigating the establishment of polarity and its requirement for later embryogenesis. However, the transduction pathways involved in the initiation of polarization are still poorly understood, and the link between the early polarization processes and embryo long-term patterning has never been experimentally demonstrated. We, therefore, have investigated the putative role of protein phosphorylation in the regulation of early embryogenesis, using a combined pharmacological and biochemical approach. Among the various protein kinase inhibitors tested, a subset of well-known PTK inhibitors, including genistein, prevented germination but had no effect on growth of germinated zygotes and embryos. Inhibition of germination appeared to be a direct consequence of prevention of polarization since genistein and other PTK inhibitors specifically inhibited axis formation in a light-independent manner. Genistein inhibited cellular events associated with polarization such as polarized secretion of cell wall sulfated compounds. Anchorage of F-actin at the rhizoid pole was also inhibited and P-actin redistributed in response to a near light vector. Zygotes inhibited in the polarization process over the period of axis formation recovered from the treatment and displayed differentiated cellular structures after a few days. However, they exhibited a deeply disorganized pattern, suggesting that the early polarization process is essential for normal patterning of the embryo. Western blot analysis of protein phosphorylation showed that the patterns of protein phosphorylation changed during development and were disturbed by treatments with genistein. This drug also inhibited in vitro autophosphorylation. The nature of the genistein-sensitive kinases required for polarizati

关键词：肌动蛋白类/代谢细胞极性/药物作用细胞极性/辐射效应细胞壁/药物作用细胞壁/代谢酶抑制剂/药理学染料木黄酮/药理学光磷酰化植物蛋白质类/代谢蛋白酪氨酸激酶类/拮抗剂和抑制剂信号传导硫酸盐类/代谢合子/细胞学合子/药物作用合子/代谢

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The bactericidal action of penicillin: new clues to an unsolved mystery

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TRENDS IN MICROBIOLOGY 2000年第6期8卷 274-278页

作者： Bayles, KW Univ Idaho Dept Microbiol Mol Biol & Biochem Moscow ID 83844 USA

The Staphylococcus aureus lrgAB operon was recently shown to inhibit extracellular murein hydrolase activity and increase tolerance to penicillin. Further characterization of this operon could provide novel insight in... 详细信息

关键词：细菌蛋白质类/代谢细胞壁/药物作用细胞壁/代谢基因表达调控/药物作用基因表达调控酶学/药物作用膜蛋白质类突变 N-乙酰胞壁酰-L-丙氨酸酰胺酶/遗传学 N-乙酰胞壁酰-L-丙氨酸酰胺酶/代谢操纵子青霉素类/药理学信号传导金黄色葡萄球菌/药物作用金黄色葡萄球菌/遗传学肺炎链球菌/药物作用肺炎链球菌/遗传学

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