No description available.

<p>The aim was to characterize 100 coagulase positive staphylococci isolates originating from pig carcasses from Swedish slaughterhouses by biotyping, antibiotic susceptibility testing, typing with pulsed field gel electrophoresis (PFGE) and real-time PCR-screening of the enterotoxin genes sea, sec, seg and sei in order to evaluate the impact on human health. The biotyping classified 56 as non host specific (NHS), 29 as human biotype, five as poultry, one as ovine, one as bovine biotype and eight were unclassified (UCF). Susceptibility testing to 16 antibiotics revealed that 49% of the isolates were resistant to penicillin, which the biotype human dominated among these isolates. The results from the PFGE showed correlation between the biotypes and the pulsotypes obtained with several groups with identical strains. The results from the 47 isolates tested for enterotoxins were that the combination of seg and sei was the most common but sea and sec were also detected. There were slaughterhouses that had certain biotypes and penicillin resistance linked to them.</p>

Background: Obesity has a strong correlation with the development of type two diabetes. As adipocytes accrue in obesity, adipose tissue may induce peripheral insulin resistance through production of pro-inflammatory cytokines and unregulated lipolysis after stimulation by endotoxin or environmental cues. In addition, obesity poses high risks of Staphylococcal aureus colonization and infection. S. aureus can cause a myriad of serious illnesses in both immunocompromised and healthy individuals. Among the S. aureus virulence factors, superantigens are essential for the organism's pathogenesis. Considering the importance of the microbiome in human illnesses, we've examined whether a staphylococcal superantigen has an impact on the development of type two diabetes via affecting adipocytes. Methodology/Principal Findings: Immortalized human adipocytes and primary rabbit adipocytes that were exposed to staphylococcal superantigen toxic shock syndrome toxin-1 (TSST-1), stimulated proinflammatory cytokine and chemokine production, and such effect could be significantly enhanced by endotoxin and other proinflammatory signals. TSST-1 also induced lipolysis in both human and rabbit adipocytes. Prolonged treatment of rabbits with subclinical doses of TSST-1 induced chronic systemic inflammation and an increase in circulating endotoxin levels, which ultimately resulted in adipocyte insulin resistance and systemic impaired glucose intolerance. Conclusions/Significance: Endotoxin has been proposed to contribute to type two diabetes through enhanced insulin resistance after chronic exposure and stimulation of adipocytes to produce cytokines. Our data indicate that staphylococcal superantigen(s) can also induce proinflammatory cytokine production and lipolysis in adipocytes. In addition, rabbits, which are chronically exposed to superantigens, experience asymptomatic systemic inflammation, high circulating endotoxin levels, and glucose metabolism deficiency that are common symptoms observed in type two diabetic patients. This is the first study that has shown that bacterial exotoxins, like S. aureus superantigen, may directly contribute to the development of type two diabetes.

Self-stabilizing polyacrylate nanoparticle emulsions were previously investigated in the Turos laboratory, and provided a new model for delivering antibiotics via encapsulation or covalent binding of the desired bioactive compound within the polymer nanoparticles. The method used the in water, free radical emulsion polymerization of butyl acrylate/styrene mixture to form the polymer chain stabilized with a surfactant. Current research in this dissertation further explores the versatility of related nanoparticle emulsion systems. Chapter 2 provides an overview of the loading of certain therapeutic drugs, such as 5-aminosalicylic acid and derivatives thereof, for the treatment of irritable bowel syndrome. Chapter 3 explores homo-polymer nanoparticle emulsions composed of menthyl acrylate as the monomer. Thereby obviating the need for a copolymer emulsion polymerization. The homo(menthyl acrylate) nanoparticle emulsion provided greater stability compared to the previous copolymer models. The resulting homopolymer emulsion exhibited a decrease in cytotoxicity, and a 400% increase for loading of penicillin G. Chapter 4 explores novel polyacrylamide nanoparticle emulsion using only N-acrylated ciprofloxacin to form a homo-polymer polyacrylate nanoparticle emulsion, thereby requiring no additional co-monomers. The resulting emulsion has a relatively low cytotoxicity with similar bioactivity to free ciprofloxacin.

<p>Staphylococcus aureus is an important human and animal pathogen that causes a wide range of infections. These infections can be very serious and sometimes hard to get rid of, because of the many virulence factors the bacteria produce during infections.</p><p>This project was a research of the extracellular fibrinogen-binding protein, Efb, which is a 15.9 kDa protein that has been shown to be an important virulence factor during S. aureus infections.</p><p>The purpose with the project was to find out if the protein has more than one binding site to fibrinogen and if people produce antibodies against Efb.</p><p>This was performed with methods such as affinity chromatography, ELISA, coagulation test and western blot. It was shown that Efb has two binding sites to fibrinogen. One is placed on the C-terminal part of Efb and the other on the N-terminal. It was also shown that the production of antibodies against Efb rises significantly in people during an ongoing infection.</p>

<p>Controlling bacterial infections with antibiotics is central to modern health care. However, increasing bacterial resistance to antibiotics threatens effective therapy. This thesis concerns the use of the antibiotic fusidic acid, and novel analogues of fusidic acid, to treat topical infections caused by the bacterial pathogen <i>Staphylococcu aureus</i>. It also addresses genetic mechanisms by which <i>S. aureus</i> develops resistance to fusidic acid.</p><p>Pre-clinical microbiological tests were made on two structurally different groups of fusidic acid analogues developed by Leo Pharma. These drugs were tested against <i>S. aureus</i> and <i>Streptococcus pyogenes</i> strains, measuring MIC, <i>in vitro</i> concentration-dependent bacteriocidal or bacteriostatic effects, and <i>in vivo</i> efficacy in clearing topical infections. We developed a new superficial skin infection animal model (the ‘tape-stripping model’) designed for testing topical antibiotics, including the novel fusidic acid analogues, against <i>S. aureus</i> and <i>S. pyogenes</i>. Some new compounds giving promising results will be further tested and developed by Leo Pharma. </p><p>Fusidic acid inhibits protein synthesis by binding to elongation factor EF-G on the ribosome. Previously described resistance mechanisms are mutations in the gene coding for EF-G (<i>fusA</i>), or, in some strains, the presence of a gene (<i>fusB, fusC</i> or <i>fusD</i>) coding for a protein that protects EF-G from fusidic acid.</p><p>We discovered two novel classes of spontaneous FusR mutants in <i>S. aureus</i> with the small colony variant (SCV) phenotype which is associated with persistent infections. The FusR SCV’s are very frequent, slow growing, cross-resistant to aminoglycosides, and auxotrophic for hemin or menadione. Some of the FusR SCV mutations are in structural domain V of EF-G (classic <i>fusA</i> mutations map overwhelmingly in domain III). The remaining FusR SCV’s are unmapped but their additive effect on MIC together with the <i>fusB</i> plasmid suggests the possibility that their mechanism of resistance is also associated with the translation machinery. </p>

Controlling bacterial infections with antibiotics is central to modern health care. However, increasing bacterial resistance to antibiotics threatens effective therapy. This thesis concerns the use of the antibiotic fusidic acid, and novel analogues of fusidic acid, to treat topical infections caused by the bacterial pathogen Staphylococcu aureus. It also addresses genetic mechanisms by which S. aureus develops resistance to fusidic acid. Pre-clinical microbiological tests were made on two structurally different groups of fusidic acid analogues developed by Leo Pharma. These drugs were tested against S. aureus and Streptococcus pyogenes strains, measuring MIC, in vitro concentration-dependent bacteriocidal or bacteriostatic effects, and in vivo efficacy in clearing topical infections. We developed a new superficial skin infection animal model (the ‘tape-stripping model’) designed for testing topical antibiotics, including the novel fusidic acid analogues, against S. aureus and S. pyogenes. Some new compounds giving promising results will be further tested and developed by Leo Pharma. Fusidic acid inhibits protein synthesis by binding to elongation factor EF-G on the ribosome. Previously described resistance mechanisms are mutations in the gene coding for EF-G (fusA), or, in some strains, the presence of a gene (fusB, fusC or fusD) coding for a protein that protects EF-G from fusidic acid. We discovered two novel classes of spontaneous FusR mutants in S. aureus with the small colony variant (SCV) phenotype which is associated with persistent infections. The FusR SCV’s are very frequent, slow growing, cross-resistant to aminoglycosides, and auxotrophic for hemin or menadione. Some of the FusR SCV mutations are in structural domain V of EF-G (classic fusA mutations map overwhelmingly in domain III). The remaining FusR SCV’s are unmapped but their additive effect on MIC together with the fusB plasmid suggests the possibility that their mechanism of resistance is also associated with the translation machinery.

The aim was to characterize 100 coagulase positive staphylococci isolates originating from pig carcasses from Swedish slaughterhouses by biotyping, antibiotic susceptibility testing, typing with pulsed field gel electrophoresis (PFGE) and real-time PCR-screening of the enterotoxin genes sea, sec, seg and sei in order to evaluate the impact on human health. The biotyping classified 56 as non host specific (NHS), 29 as human biotype, five as poultry, one as ovine, one as bovine biotype and eight were unclassified (UCF). Susceptibility testing to 16 antibiotics revealed that 49% of the isolates were resistant to penicillin, which the biotype human dominated among these isolates. The results from the PFGE showed correlation between the biotypes and the pulsotypes obtained with several groups with identical strains. The results from the 47 isolates tested for enterotoxins were that the combination of seg and sei was the most common but sea and sec were also detected. There were slaughterhouses that had certain biotypes and penicillin resistance linked to them.

Staphylococcus aureus is an important human and animal pathogen that causes a wide range of infections. These infections can be very serious and sometimes hard to get rid of, because of the many virulence factors the bacteria produce during infections. This project was a research of the extracellular fibrinogen-binding protein, Efb, which is a 15.9 kDa protein that has been shown to be an important virulence factor during S. aureus infections. The purpose with the project was to find out if the protein has more than one binding site to fibrinogen and if people produce antibodies against Efb. This was performed with methods such as affinity chromatography, ELISA, coagulation test and western blot. It was shown that Efb has two binding sites to fibrinogen. One is placed on the C-terminal part of Efb and the other on the N-terminal. It was also shown that the production of antibodies against Efb rises significantly in people during an ongoing infection.

No description available.