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[PMID]: 29385201 [Au] Autor: Zhou Z; Liu F; Zhang X; Zhou X; Zhong Z; Su H; Li J; Li H; Feng F; Lan J; Zhang Z; Fu H; Hu Y; Cao S; Chen W; Deng J; Yu J; Zhang W; Peng G [Ad] Endereço: The Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China. [Ti] Título: Cellulose-dependent expression and antibacterial characteristics of surfactin from Bacillus subtilis HH2 isolated from the giant panda. [So] Source: PLoS One;13(1):e0191991, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Surfactin secreted by Bacillus subtilis can confer strong, diverse antipathogenic effects, thereby benefitting the host. Carbon source is an important factor for surfactin production. However, the mechanism that bacteria utilize cellulose, the most abundant substance in the intestines of herbivores, to produce surfactin remains unclear. Here, we used B. subtilis HH2, isolated from the feces of a giant panda, as a model to determine changes in surfactin expression in the presence of different concentrations of cellulose by quantitative polymerase chain reaction and high-performance liquid chromatography. We further investigated the antimicrobial effects of surfactin against three common intestinal pathogens (Escherichia coli, Staphylococcus aureus, and Salmonella enterica) and its resistance to high temperature (60-121°C), pH (1-12), trypsin (100-300 µg/mL, pH 8), and pepsin (100-300 µg/mL, pH 2). The results showed that the surfactin expressed lowest in bacteria cultured in the presence of 1% glucose medium as the carbon source, whereas increased in an appropriate cellulose concentration (0.67% glucose and 0.33% cellulose). The surfactin could inhibit E. coli and Staphylococcus aureus, but did not affect efficiently for Salmonella enterica. The antibacterial ability of surfactin did not differ according to temperature (60-100°C), pH (2-11), trypsin (100-300 µg/mL), and pepsin (100-300 µg/mL; P > 0.05), but decreased significantly at extreme environments (121°C, pH 1 or 12; P < 0.05) compared with that in the control group (37°C, pH = 7, without any protease). In conclusion, our findings indicated that B. subtilis HH2 could increase surfactin expression in an appropriate cellulose environment and thus provide benefits to improve the intestinal health of herbivores. [Mh] Termos MeSH primário: Antibacterianos/metabolismo Bacillus subtilis/metabolismo Celulose/metabolismo Lipopeptídeos/metabolismo [Mh] Termos MeSH secundário: Animais Antibacterianos/farmacologia Meios de Cultura Lipopeptídeos/farmacologia Ursidae [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Anti-Bacterial Agents); 0 (Culture Media); 0 (Lipopeptides); 9004-34-6 (Cellulose) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180309 [Lr] Data última revisão: 180309 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180201 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0191991

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[PMID]: 29442037 [Au] Autor: Seko T; Usami E; Kimura M; Nakao T; Matsuoka T; Yoshimura T; Kanamori N; Tachi T; Teramachi H [Ti] Título: A comparative analysis of micafungin and caspofungin for empirical antifungal therapy in antibiotic-unresponsive febrile patients with hematologic malignancies. [So] Source: Pharmazie;71(8):484-488, 2016 Aug 01. [Is] ISSN: 0031-7144 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: This study was retrospectively carried out to compare the efficacy of echinocandins such as micafungin (MCFG) and caspofungin (CPFG) in the treatment of antibiotic-unresponsive febrile patients with hematologic malignancies. A total of 163 patients received either MCFG or CPFG. We evaluated the efficacy of echinocandin against fever decline in all patients. Fever decline, defined as a body temperature of less than 37.5 °C sustained for more than 48 h without scheduled antipyretic medication. Efficacy assessments showed that the incidence of fever decline was not significantly different between the MCFG and CPFG groups (P=0.599). The median number of days from the start of echinocandin administration to fever decline was 5 in both the MCFG and CPFG groups. Multivariate analysis showed that the use of anti-MRSA drugs (HR, 0.64; 95%CI, 0.45-0.90; P=0.011) and a change from echinocandins to voriconazole or liposomal-amphotericin B (HR, 0.50; 95%CI, 0.30-0.74; P<0.001) are significant risk factors for sustained fever. A significant difference (P=0.002) in incidence of fever decline was however associated with differences in the timing of anti-MRSA drug administration. The median number of days from the start of echinocandin administration to fever decline was 5 when administration of the anti-MRSA drug occurred "simultaneously or prior to echinocandin start" and 11 in the "next day or later of echinocandin start" group. In other words, starting anti-MRSA drug treatment after echinocandin treatment is a risk factor. In conclusion, MCFG and CPFG have similar efficacy as empirical antifungal agents in the treatment of antibioticunresponsive febrile patients with hematopoietic malignancies. [Mh] Termos MeSH primário: Antifúngicos/uso terapêutico Equinocandinas/uso terapêutico Febre/tratamento farmacológico Febre/etiologia Neoplasias Hematológicas/complicações Lipopeptídeos/uso terapêutico Micoses/tratamento farmacológico [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Farmacorresistência Fúngica Feminino Seres Humanos Masculino Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos Meia-Idade Micoses/complicações Estudos Retrospectivos Fatores de Risco Infecções Estafilocócicas/tratamento farmacológico Adulto Jovem [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Echinocandins); 0 (Lipopeptides); F0XDI6ZL63 (caspofungin); R10H71BSWG (micafungin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180307 [Lr] Data última revisão: 180307 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180215 [St] Status: MEDLINE [do] DOI: 10.1691/ph.2016.6612

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[PMID]: 28595450 [Au] Autor: Jiang W; Zhou W; Othman R; Uchida H; Watanabe R; Suzuki T; Sakamoto B; Nagai H [Ad] Endereço: a Department of Ocean Sciences , Tokyo University of Marine Science and Technology , Tokyo , Japan. [Ti] Título: A new malyngamide from the marine cyanobacterium Moorea producens. [So] Source: Nat Prod Res;32(1):97-104, 2018 Jan. [Is] ISSN: 1478-6427 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: A new malyngamide (1) was isolated along with seven known compounds (2-8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10-100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides. [Mh] Termos MeSH primário: Cianobactérias/química Lipopeptídeos/química Lipopeptídeos/farmacologia [Mh] Termos MeSH secundário: Amidas/química Amidas/farmacologia Animais Organismos Aquáticos/química Linhagem Celular Tumoral Leucemia L1210 Espectroscopia de Ressonância Magnética Camundongos Estrutura Molecular Palaemonidae/efeitos dos fármacos Pirróis/química Pirróis/farmacologia Relação Estrutura-Atividade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amides); 0 (Lipopeptides); 0 (Pyrroles); 0 (isomalyngamide A); 0 (isomalyngamide B) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180301 [Lr] Data última revisão: 180301 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170610 [St] Status: MEDLINE [do] DOI: 10.1080/14786419.2017.1338282

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[PMID]: 29384927 [Au] Autor: Ji Y; Song Y; Zhou F; Liu T; Jiang M; Zhao X; Huang X [Ad] Endereço: Beijing United Family Hospital. [Ti] Título: Efficacy and safety of micafungin for the treatment of patients with proven or probable invasive aspergillosis: A non-comparative, multicenter, phase IV, open-label study. [So] Source: Medicine (Baltimore);96(52):e9443, 2017 Dec. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Few studies have assessed the efficacy and safety of micafungin in patients with proven or probable invasive aspergillosis (IA). This was the aim of the current study, which was conducted in 22 hospitals in China, where micafungin was approved for treatment of IA in 2006. METHODS: This was a non-comparative, phase IV open-label study (NCT02646774). Eligible patient were adults with proven or probable IA. Efficacy endpoints included rates of overall treatment success (primary endpoint) and clinical improvement, fungal clearance, mortality, and the site of Aspergillus infection (all secondary endpoints). Safety endpoints included incidences of treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and adverse drug reactions (ADRs). These endpoints were reported descriptively with associated 95% confidence intervals (CI); no hypotheses were tested. RESULTS: The study was discontinued early due to low patient recruitment, which did not allow for the planned sample size to be reached. In total, 68 patients were enrolled: 42 into the full analysis set (for efficacy) and 61 into the safety analysis set. All patients were Han Chinese; the majority were male (n = 26; 61.9%) and ≤60 years of age (n = 35; 83.3%). Rates of overall treatment success, clinical improvement, fungal clearance, and mortality were 45.2% (n = 19/42; 95% CI: 29.85-61.33); 59.5% (n = 25/42; 95% CI: 43.28-74.37), 80.0% (n = 4/5; 95% CI: 28.36-99.49), and 7.1% (n = 3/42; 95% CI: 1.50-19.48), respectively. All patients were diagnosed with pulmonary Aspergillus infection. Overall, 155 TEAEs and 8 SAEs were reported by 37 (60.7%) and 7 (11.5%) patients. The most common TEAEs were decreased platelet count and fatigue (both n = 5; 8.2%) and the most common SAEs were intracranial hemorrhage and lung infection (n = 3; 4.9% and n = 2; 3.3%). Eight ADRs (n = 6; 9.8%) were reported but all were completely remitted or remitting during follow-up. CONCLUSIONS: Results suggest that micafungin is efficacious and well-tolerated in patients with proven or probable IA in China. However, these findings should be interpreted with care, due to the small number of patients included in this study. Further comparative trials should be used to confirm the efficacy and safety of micafungin in patients with proven or probable IA. [Mh] Termos MeSH primário: Antifúngicos/uso terapêutico Aspergilose/tratamento farmacológico Equinocandinas/uso terapêutico Lipopeptídeos/uso terapêutico [Mh] Termos MeSH secundário: Adulto Idoso Aspergilose/diagnóstico Aspergilose/mortalidade China Relação Dose-Resposta a Droga Feminino Seres Humanos Masculino Meia-Idade Resultado do Tratamento Adulto Jovem [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE IV; JOURNAL ARTICLE; MULTICENTER STUDY [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Echinocandins); 0 (Lipopeptides); R10H71BSWG (micafungin) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180228 [Lr] Data última revisão: 180228 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180201 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009443

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[PMID]: 28744860 [Au] Autor: Patil A; Majumdar S [Ad] Endereço: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, MS, USA. [Ti] Título: Echinocandins in antifungal pharmacotherapy. [So] Source: J Pharm Pharmacol;69(12):1635-1660, 2017 Dec. [Is] ISSN: 2042-7158 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVES: Echinocandins are the newest addition of the last decade to the antifungal armamentarium, which, owing to their unique mechanism of action, selectively target the fungal cells without affecting mammalian cells. Since the time of their introduction, they have come to occupy an important niche in the antifungal pharmacotherapy, due to their efficacy, safety, tolerability and favourable pharmacokinetic profiles. This review deals with the varying facets of echinocandins such as their chemistry, in-vitro and in-vivo evaluations, clinical utility and indications, pharmacokinetic and pharmacodynamic profiles, and pharmacoeconomic considerations. KEY FINDINGS: Clinical studies have demonstrated that the echinocandins - caspofungin, micafungin and anidulafungin - are equivalent, if not superior, to the mainstay antifungal therapies involving amphotericin B and fluconazole. Moreover, echinocandin regimen has been shown to be more cost-effective and economical. Hence, the echinocandins have found favour in the management of invasive systemic fungal infections. CONCLUSIONS: The subtle differences in echinocandins with respect to their pharmacology, clinical therapy and the mechanisms of resistance are emerging at a rapid pace from the current pool of research which could potentially aid in extending their utility in the fungal infections of the eye, heart and nervous system. [Mh] Termos MeSH primário: Antifúngicos/farmacologia Equinocandinas/farmacologia Lipopeptídeos/farmacologia Micoses/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Farmacorresistência Fúngica Equinocandinas/efeitos adversos Equinocandinas/farmacocinética Seres Humanos Lipopeptídeos/efeitos adversos Lipopeptídeos/farmacocinética [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Echinocandins); 0 (Lipopeptides); 9HLM53094I (anidulafungin); F0XDI6ZL63 (caspofungin); R10H71BSWG (micafungin) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180201 [Lr] Data última revisão: 180201 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170727 [St] Status: MEDLINE [do] DOI: 10.1111/jphp.12780

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[PMID]: 28471450 [Au] Autor: Zhong J; Wang H; Chen W; Sun Z; Chen J; Xu Y; Weng M; Shi Q; Ma D; Miao C [Ad] Endereço: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China. [Ti] Título: Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways. [So] Source: Cell Death Dis;8(5):e2763, 2017 May 04. [Is] ISSN: 2041-4889 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Sepsis is a systemic inflammation caused by infection. The balance between M1-M2 macrophage polarization has an essential role in the pathogenesis of sepsis. However, the exact mechanism underlying macrophage polarization is unclear. We previously showed that levels of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) were significantly elevated in septic patients compared with those in nonseptic patients, and involved in the activation of Toll-like receptor (TLR) 2/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB pathway. In the present study, we explored whether MFHAS1 was involved in macrophage polarization and determined the effect of MFHAS1 on inflammation. We performed in vitro pulldown assays and in vivo co-immunoprecipitation assays and found that E3 ubiquitin ligase praja2 could directly bind to MFHAS1. In situ immunostaining analysis confirmed the colocalization of endogenous praja2 with MFHAS1. We first reported that praja2 promotes the accumulation of ubiquitylated MFHAS1 but does not degrade it. Moreover, our results indicate that MFHAS1 ubiquitylation by praja2 positively regulates TLR2-mediated JNK/p38 pathway and promotes M1 macrophage polarization, M2 to M1 macrophage transformation and inflammation. [Mh] Termos MeSH primário: Proteínas de Ciclo Celular/metabolismo Proteínas de Ligação a DNA/metabolismo Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo Proteínas Oncogênicas/metabolismo Ubiquitina-Proteína Ligases/metabolismo Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo [Mh] Termos MeSH secundário: Animais Proteínas de Ciclo Celular/química Proteínas de Ciclo Celular/genética Polaridade Celular/efeitos dos fármacos Proteínas de Ligação a DNA/química Proteínas de Ligação a DNA/genética Células HEK293 Seres Humanos Imidazóis/farmacologia Inflamação/metabolismo Inflamação/patologia Interleucina-6/genética Interleucina-6/metabolismo Lipopeptídeos/farmacologia Macrófagos/citologia Macrófagos/efeitos dos fármacos Macrófagos/metabolismo Camundongos Óxido Nítrico Sintase Tipo II/genética Óxido Nítrico Sintase Tipo II/metabolismo Proteínas Oncogênicas/química Proteínas Oncogênicas/genética Piridinas/farmacologia Células RAW 264.7 Transdução de Sinais/efeitos dos fármacos Receptor 2 Toll-Like/metabolismo Fator de Necrose Tumoral alfa/genética Fator de Necrose Tumoral alfa/metabolismo Ubiquitina-Proteína Ligases/química Ubiquitinação/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cell Cycle Proteins); 0 (DNA-Binding Proteins); 0 (Imidazoles); 0 (Interleukin-6); 0 (Lipopeptides); 0 (MFHAS1 protein, human); 0 (Oncogene Proteins); 0 (Pam(3)CSK(4) peptide); 0 (Pyridines); 0 (Toll-Like Receptor 2); 0 (Tumor Necrosis Factor-alpha); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 2.3.2.27 (PJA2 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); OU13V1EYWQ (SB 203580) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180129 [Lr] Data última revisão: 180129 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170505 [St] Status: MEDLINE [do] DOI: 10.1038/cddis.2017.102

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[PMID]: 29261777 [Au] Autor: Noll F; Behnke J; Leiting S; Troidl K; Alves GT; Müller-Redetzky H; Preissner KT; Fischer S [Ad] Endereço: Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany. [Ti] Título: Self-extracellular RNA acts in synergy with exogenous danger signals to promote inflammation. [So] Source: PLoS One;12(12):e0190002, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Self-extracellular RNA (eRNA), released from stressed or injured cells upon various pathological situations such as ischemia-reperfusion-injury, has been shown to act as an alarmin by inducing procoagulatory and proinflammatory responses. In particular, M1-polarization of macrophages by eRNA resulted in the expression and release of a variety of cytokines, including tumor necrosis factor (TNF)-α or interleukin-6 (IL-6). The present study now investigates in which way self-eRNA may influence the response of macrophages towards various Toll-like receptor (TLR)-agonists. Isolated agonists of TLR2 (Pam2CSK4), TLR3 (PolyIC), TLR4 (LPS), or TLR7 (R848) induced the release of TNF-α in a concentration-dependent manner in murine macrophages, differentiated from bone marrow-derived stem cells by mouse colony stimulating factor. Here, the presence of eRNA shifted the dose-response curve for Pam2CSK4 (Pam) considerably to the left, indicating that eRNA synergistically enhanced the cytokine liberation from macrophages even at very low Pam-levels. The synergistic activation of TLR2 by eRNA/Pam was duplicated by other TLR2-agonists such as FSL-1 or Pam3CSK4. In contrast, for TLR4-agonists such as LPS a synergistic effect of eRNA was much weaker, and was not existent for TLR3-, or TLR7-agonists. The synergistic eRNA/Pam action was dependent on the NFκB-signaling pathway as well as on p38MAP- and MEK1/ERK-kinases and was prevented by predigestion of eRNA with RNase1 or by antibodies against TLR2. Thus, the presence of self-eRNA as alarming molecule sensitizes innate immune responses towards pathogen-associated molecular patterns (PAMPs) in a synergistic way and may thereby contribute to the differentiated outcome of inflammatory responses. [Mh] Termos MeSH primário: Espaço Extracelular/metabolismo Inflamação/metabolismo RNA/metabolismo Transdução de Sinais [Mh] Termos MeSH secundário: Animais Citocinas/metabolismo Diglicerídeos/farmacologia Lipopeptídeos/farmacologia Macrófagos/efeitos dos fármacos Macrófagos/metabolismo Camundongos Endogâmicos C57BL Oligopeptídeos/farmacologia Padrões Moleculares Associados a Patógenos/metabolismo Transdução de Sinais/efeitos dos fármacos Fatores de Tempo Receptores Toll-Like/antagonistas & inibidores Receptores Toll-Like/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cytokines); 0 (Diglycerides); 0 (FSL-1 lipoprotein, synthetic); 0 (Lipopeptides); 0 (Oligopeptides); 0 (Pam2CSK4 lipopeptide); 0 (Pathogen-Associated Molecular Pattern Molecules); 0 (Toll-Like Receptors); 63231-63-0 (RNA) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180108 [Lr] Data última revisão: 180108 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171221 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0190002

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[PMID]: 28454673 [Au] Autor: Becker B; Butler MS; Hansford KA; Gallardo-Godoy A; Elliott AG; Huang JX; Edwards DJ; Blaskovich MAT; Cooper MA [Ad] Endereço: Institute of Molecular Bioscience, University of Queensland, Brisbane 4072, Australia. [Ti] Título: Synthesis of octapeptin C4 and biological profiling against NDM-1 and polymyxin-resistant bacteria. [So] Source: Bioorg Med Chem Lett;27(11):2407-2409, 2017 06 01. [Is] ISSN: 1464-3405 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The first synthesis of octapeptin C4 was achieved using a combination of solid phase synthesis and off-resin cyclisation. Octapeptin C4 displayed antibiotic activity against multi-drug resistant, NDM-1 and polymyxin-resistant Gram-negative bacteria, with moderate activity against Staphylococcus aureus. The linear analogue of octapeptin C4 was also prepared, which showed reduced activity. [Mh] Termos MeSH primário: Antibacterianos/farmacologia Lipopeptídeos/farmacologia Peptídeos Cíclicos/farmacologia [Mh] Termos MeSH secundário: Antibacterianos/síntese química Antibacterianos/toxicidade Ciclização Farmacorresistência Bacteriana Bactérias Gram-Negativas/efeitos dos fármacos Lipopeptídeos/síntese química Lipopeptídeos/toxicidade Peptídeos Cíclicos/síntese química Peptídeos Cíclicos/toxicidade Polimixina B/farmacologia Técnicas de Síntese em Fase Sólida Staphylococcus aureus/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Anti-Bacterial Agents); 0 (Lipopeptides); 0 (Peptides, Cyclic); 0 (octapeptin C4); 1404-26-8 (Polymyxin B) [Em] Mês de entrada: 1712 [Cu] Atualização por classe: 180105 [Lr] Data última revisão: 180105 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170430 [St] Status: MEDLINE

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[PMID]: 28961818 [Au] Autor: Asari S; Ongena M; Debois D; De Pauw E; Chen K; Bejai S; Meijer J [Ad] Endereço: Department of Plant Biology, Uppsala Biocenter, Linnéan Center for Plant Biology, Swedish University of Agricultural Sciences, S-75007 Uppsala, Sweden. [Ti] Título: Insights into the molecular basis of biocontrol of Brassica pathogens by Bacillus amyloliquefaciens UCMB5113 lipopeptides. [So] Source: Ann Bot;120(4):551-562, 2017 Oct 17. [Is] ISSN: 1095-8290 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Background and Aims: Certain micro-organisms can improve plant protection against pathogens. The protective effect may be direct, e.g. due to antibiotic compounds, or indirect, by priming of plant defence as induced systemic resistance (ISR). The plant growth-promoting rhizobacterium Bacillus amyloliquefaciens UCMB5113 shows potential for disease management of oilseed rape. To investigate the mode of action of this protection, especially in relation to jasmonic acid-dependent ISR, Bacillus UCMB5113 was tested with Arabidopsis thaliana mutants and several important fungal pathogens of Brassica species. Methods: Secreted lipopeptide fractions from Bacillus UCMB5113, together with synthetic peptide mimics, were evaluated for their effects on fungal phytopathogens and A. thaliana . The structures of secreted lipopeptides were analysed using mass spectrometry. Plant mutants and reporter lines were used to identify signalling steps involved in disease suppression by lipopeptides. Key Results: In plate tests Bacillus UCMB5113 and lipopeptide extracts suppressed growth of several fungal pathogens infecting Brassica plants. Separation of secreted lipopeptides using reversed-phase high-performance liquid chromatography revealed several fractions that inhibited fungal growth. Analysis by mass spectrometry identified the most potent compounds as novel linear forms of antifungal fengycins, with synthetic peptide mimics confirming the biological activity. Application of the lipopeptide extracts on Arabidopsis roots provided systemic protection against Alternaria brassicicola on leaves. Arabidopsis signalling mutants and PDF1.2 and VSP2 promoter-driven GUS lines indicated that the lipopeptide fraction involved jasmonic-acid-dependent host responses for suppression of fungal growth indicative of ISR. Conclusions: The ability of Bacillus UCMB5113 to counteract pathogens using both antagonistic lipopeptides and through ISR provides a promising tool for sustainable crop production. [Mh] Termos MeSH primário: Bacillus amyloliquefaciens/fisiologia Brassica/microbiologia Resistência à Doença/fisiologia Lipopeptídeos/fisiologia [Mh] Termos MeSH secundário: Alternaria/metabolismo Antifúngicos/metabolismo Arabidopsis/microbiologia Arabidopsis/fisiologia Bacillus amyloliquefaciens/metabolismo Brassica/fisiologia Interações Hospedeiro-Patógeno/fisiologia Folhas de Planta/microbiologia Folhas de Planta/fisiologia Raízes de Plantas/microbiologia Raízes de Plantas/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Lipopeptides) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171109 [Lr] Data última revisão: 171109 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170930 [St] Status: MEDLINE [do] DOI: 10.1093/aob/mcx089

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[PMID]: 28934373 [Au] Autor: Winther M; Holdfeldt A; Sundqvist M; Rajabkhani Z; Gabl M; Bylund J; Dahlgren C; Forsman H [Ad] Endereço: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [Ti] Título: Formyl peptide derived lipopeptides disclose differences between the receptors in mouse and men and call the pepducin concept in question. [So] Source: PLoS One;12(9):e0185132, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: A pepducin is a lipopeptide containing a peptide sequence that is identical to one of the intracellular domains of the G-protein coupled receptor (GPCR) assumed to be the target. Neutrophils express two closely related formyl peptide receptors belonging to the family of GPCRs; FPR1 and FPR2 in human and their respective orthologue Fpr1 and Fpr2 in mouse. By applying the pepducin concept, we have earlier identified FPR2 activating pepducins generated from the third intracellular loop of FPR2. The third intracellular loop of FPR2 differs in two amino acids from that of FPR1, seven from Fpr2 and three from Fpr1. Despite this, we found that pepducins generated from FPR1, FPR2, Fpr1 and Fpr2 all targeted FPR2 in human neutrophils and Fpr2 in mouse, but with different modulating outcomes. Whereas the FPR1/Fpr1 derived pepducins inhibited the FPR2 function in human neutrophils, they activated Fpr2 in mouse. The FPR2 derived pepducin activated FPR2/Fpr2, whereas the pepducin generated from Fpr2 inhibited both FPR2 and Fpr2. In summary, our data demonstrate that pepducins generated from the third intracellular loop of human FPR1/2 and mouse Fpr1/2, all targeted FPR2 in human and Fpr2 in mouse. With respect to the modulating outcomes, pepducin inhibitors identified for FPR2 are in fact activators for Fpr2 in mouse neutrophils. Our data thus questions the validity of pepducin concept regarding their receptor selectivity but supports the notion that FPR2/Fpr2 may recognize a lipopeptide molecular pattern, and highlight the differences in ligand recognition profile between FPR2 and its mouse orthologue Fpr2. [Mh] Termos MeSH primário: Lipopeptídeos/metabolismo Receptores de Formil Peptídeo/metabolismo Receptores de Lipoxinas/metabolismo [Mh] Termos MeSH secundário: Animais Seres Humanos Leucócitos/metabolismo Lipopeptídeos/administração & dosagem Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout Modelos Moleculares NADPH Oxidases/metabolismo Ligação Proteica Receptores de Formil Peptídeo/genética Especificidade da Espécie [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (FPR1 protein, human); 0 (FPR2 protein, human); 0 (Fpr1 protein, mouse); 0 (Lipopeptides); 0 (Receptors, Formyl Peptide); 0 (Receptors, Lipoxin); 0 (formyl peptide receptor 2, mouse); EC 1.6.3.- (NADPH Oxidases) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170922 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0185132

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