RESUMO
Actinobacillus pleuropneumoniae is the causative agent of severe necrotizing pneumonia in swine. Previously, we identified the ohr gene encoding organic hydroperoxide reductase as specifically induced during infection of pigs, induced in vitro by organic peroxides but not other oxygen radicals, and present in A. pleuropneumoniae serotypes 1, 9 and 11 but not in other serotypes (Shea & Mulks, 2002). Through analysis of flanking genomic sequence, we identify a homologue of gst, which encodes glutathione-S-transferase, immediately downstream of ohr and demonstrate that ohr-gst confers low but uninducible Ohr activity to serotype 5. We further identify a genomic island of 9.3 kb, flanked by lysR and araC homologues, in serotypes 1, 9 and 11, which contains ohr and gst. In serotypes 2-8, 10 and 12, this region of the genome contains a 1.1-kb islet with a putative transposase flanked by lysR and araC.
Assuntos
Actinobacillus pleuropneumoniae/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Ilhas Genômicas , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Peroxidases/genética , Peroxidases/metabolismo , Actinobacillus pleuropneumoniae/isolamento & purificação , Animais , DNA Bacteriano/química , DNA Bacteriano/genética , Ordem dos Genes , Dados de Sequência Molecular , Análise de Sequência de DNA , Suínos/microbiologiaRESUMO
Streptococcus suis is an important swine pathogen and a zoonotic agent. Differences in virulence have been noted among the 33 described serotypes, serotype 2 being considered the most virulent. In this study, we aimed at assessing the serotype distribution and the production of virulence-associated markers by strains recovered from diseased pigs in the United States (U.S.). Results showed that among the 100 strains evaluated, serotype 3 (20% of the isolates) and serotype 2 (17%) were the most prevalent. We then investigated the presence in these isolates of the genes sly, epf and mrp, encoding the virulence-associated markers suilysin (SLY), extracellular factor (EF) and muramidase-released (MRP) protein, respectively. The effective production of the markers by the strains was also verified. Results showed that the presence of the gene did not always correlate with actual expression of the respective protein. In the case of MRP, this was due, in most cases, to frameshift mutations at the 5' end of the gene resulting in premature stop codons. The most prevalent phenotypes among U.S. strains were MRP(+)EF(-)SLY(-) (40%) and MRP(-)EF(-)SLY(+) (35%). Serotype distribution greatly differed from that reported in several European countries, as did the production of virulence markers, particularly for serotype 2. On the other hand, our results for the U.S. S. suis isolates are similar to those reported for Canadian strains, suggesting a common status in North America.
Assuntos
Infecções Estreptocócicas/veterinária , Streptococcus suis/classificação , Streptococcus suis/patogenicidade , Doenças dos Suínos/microbiologia , Animais , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Muramidase/genética , Muramidase/metabolismo , Fenótipo , Sorotipagem , Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Sus scrofa , Estados Unidos , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
Cholesterol absorption inhibition (CAI) represents an important treatment option for hypercholesterolemia. Herein, we report the design and evaluation of a series of substituted oxazolidinones as ligands for the Niemann Pick C1 Like 1 (NPC1L1) protein, a key mediator of cholesterol transport. Novel analogs were initially evaluated in a brush border membrane NPC1L1 binding assay; subsequently, promising compounds were evaluated in vivo for acute inhibition of cholesterol absorption. These studies identified analogs with low micromolar NPC1L1 binding affinity and acute in vivo efficacy of >50% absorption inhibition at 3mg/kg.
