RESUMEN
Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.
Asunto(s)
Adamantano , Aminobenzoatos , Aminofenoles , Anilidas , Compuestos Policíclicos , Aminofenoles/química , Aminofenoles/farmacología , Aminofenoles/síntesis química , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/síntesis química , Adamantano/química , Adamantano/farmacología , Adamantano/síntesis química , Adamantano/análogos & derivados , Anilidas/farmacología , Anilidas/química , Anilidas/síntesis química , Aminobenzoatos/farmacología , Aminobenzoatos/química , Aminobenzoatos/síntesis química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Estructura Molecular , Reacción de Cicloadición , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/químicaRESUMEN
Kounis syndrome is defined as an acute coronary syndrome (ACS) secondary to allergic or hypersensitivity reactions. It can be further categorised into subtypes such as coronary vasospasms, acute myocardial infarction or stent thrombosis based on the pathogenesis. Kounis syndrome is most likely an underdiagnosed condition in China, given the many triggers reported in the literature. Herein, we report a case of Kounis syndrome, possibly triggered by a bee sting. The patient had late onset of angina symptoms with delayed diagnosis due to unfamiliarity with this condition. In patients with clinical signs of ACS that are superimposed on a hypersensitivity reaction, especially those with pre-existing cardiovascular risk factors, Kounis syndrome should be considered, so that appropriate assessment and treatment can be initiated. Prompt management of both the allergic reaction and the ACS is vital for Kounis syndrome.
Asunto(s)
Síndrome Coronario Agudo , Hipersensibilidad , Mordeduras y Picaduras de Insectos , Síndrome de Kounis , Infarto del Miocardio , Animales , Humanos , Abejas , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiología , Síndrome de Kounis/terapia , Mordeduras y Picaduras de Insectos/complicaciones , Mordeduras y Picaduras de Insectos/diagnóstico , Hipersensibilidad/etiología , Infarto del Miocardio/complicaciones , Angina de Pecho , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/etiologíaRESUMEN
The present study focuses on the risk rankings of different contaminants from Daling River in Liaoning Province, China, for categorizing the environmental risk levels in the river. Eighteen surface water samples were collected from Daling River, which has been polluted by the surrounding fluorine industries for years. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and heavy metals were analyzed, and relevant eco-toxicity data obtained from literatures were considered. The median concentrations of PFOS and PFOA were observed as 0.77-3.57 ng·L-1 and 82.93-344 ng·L-1, respectively, which were lower than the standard limits of the United Kingdom. The concentrations of heavy metals and organochlorine pesticides (OCPs) were found to be lower than level â £ of the Chinese national environmental quality standards for surface water. The maximum concentrations of mercury (Hg) and arsenic (As) were higher than the standard level â ¢. The environmental risks ranged from 1.42×10-6 to 2.3×10-2. The order of the risks by potential environmental contaminants was Cu > Zn > As > p,p'-DDE > p,p'-DDT > Cd > Pb > Hg > PFOA > γ-HCH > Cr > Ni > α-HCH > PFOS. The present findings revealed that the environmental risks of PFOS and PFOA were relatively low and these were not taken as priority contaminants, but the accumulation risks could not be overlooked for a long time. Among the contaminants, copper (Cu) was the priority contaminant of Daling River. Hence, necessary measures are recommended to reduce the potential effects of contaminants on the environment.
RESUMEN
Staphylococcus epidermidis strains are diverse in their pathogenicity; some are invasive and cause serious nosocomial infections, whereas others are non-pathogenic commensal organisms. To analyse the implications of different virulence factors in Staphylococcus epidermidis infections, the complete genome of Staphylococcus epidermidis strain ATCC 12228, a non-biofilm forming, non-infection associated strain used for detection of residual antibiotics in food products, was sequenced. This strain showed low virulence by mouse and rat experimental infections. The genome consists of a single 2499 279 bp chromosome and six plasmids. The chromosomal G + C content is 32.1% and 2419 protein coding sequences (CDS) are predicted, among which 230 are putative novel genes. Compared to the virulence factors in Staphylococcus aureus, aside from delta-haemolysin and beta-haemolysin, other toxin genes were not found. In contrast, the majority of adhesin genes are intact in ATCC 12228. Most strikingly, the ica operon coding for the enzymes synthesizing interbacterial cellular polysaccharide is missing in ATCC 12228 and rearrangements of adjacent genes are shown. No mec genes, IS256, IS257, were found in ATCC 12228. It is suggested that the absence of the ica operon is a genetic marker in commensal Staphylococcus epidermidis strains which are less likely to become invasive.
Asunto(s)
Biopelículas/crecimiento & desarrollo , Genoma Bacteriano , Análisis de Secuencia de ADN , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/patogenicidad , Virulencia/genética , Adhesinas Bacterianas/genética , Animales , Antibacterianos/farmacología , Toxinas Bacterianas/genética , Recuento de Colonia Microbiana , Elementos Transponibles de ADN/genética , Farmacorresistencia Bacteriana , Marcadores Genéticos , Ratones , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Polisacáridos Bacterianos/genética , Ratas , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/crecimiento & desarrolloRESUMEN
Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen.