http://hdl.handle.net/2262/136 Clinical Microbiology (Scholarly Publications) 2013-05-22T11:04:39Z http://hdl.handle.net/2262/58419 Title: Human bovine tuberculosis - remains in the differential. Author: MURPHY, PHILIP Abstract: Mycobacterium bovis is a pathogen of cattle. The unpasteurized milk of affected cattle is a source of infection in humans. Despite the screening of cattle and the pasteurization of milk, M bovis has not been eradicated. A high index of clinical suspicion is needed in symptomatic patients with a history of possible exposure. At risk groups include animal workers, farmers, meat packers, vets and zoo keepers. Humans are usually infected by the aerosol route. We present two cases of human bovine tuberculosis. One was a presumptive case and the second was a confirmed case. Both responded well to antituberculous therapy. In the confirmed case, there was evidence of transmission to the partner living in the same house. Rifampicin prophylaxis was given to the exposed case. The M. bovis from the confirmed case was isoniazid resistant, in addition to having the well known resistance to pyrazinamide. Isoniazid resistance has been described before in those who are immunocompromised. We describe it in an immunocompetent patient. Description: PUBLISHED 2010-01-01T00:00:00Z http://hdl.handle.net/2262/51424 Title: The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. Author: ROGERS, THOMAS RICHARD FRAZER; MORTON, CHARLES OLIVER Abstract: Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Monocyte-derived immature DCs (iDC) were infected with viable resting conidia of Aspergillus fumigatus (Af293) for 12 hours at an MOI of 5; cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to microarrays. iDC cell death increased at 6 h in the presence of A. fumigatus which coincided with fungal germ tube emergence; >80% of conidia were associated with iDC. Over the time course A. fumigatus differentially regulated 210 genes, FunCat analysis indicated significant up-regulation of genes involved in fermentation, drug transport, pathogenesis and response to oxidative stress. Genes related to cytotoxicity were differentially regulated but the gliotoxin biosynthesis genes were down regulated over the time course, while Aspf1 was up-regulated at 9 h and 12 h. There was an up-regulation of genes in the subtelomeric regions of the genome as the interaction progressed. The genes up-regulated by iDC in the presence of A. fumigatus indicated that they were producing a pro-inflammatory response which was consistent with previous transcriptome studies of iDC interacting with A. fumigatus germ tubes. This study shows that A. fumigatus adapts to phagocytosis by iDCs by utilising genes that allow it to survive the interaction rather than just up-regulation of specific virulence genes. Description: PUBLISHED 2011-01-01T00:00:00Z http://hdl.handle.net/2262/49838 Title: A commensal gone bad: complete genome sequence of the prototypical enterotoxigenic Escherichia coli strain H10407. Author: SMITH, STEPHEN Abstract: In most cases, Escherichia coli exists as a harmless commensal organism, but it may on occasion cause intestinal and/or extraintestinal disease. Enterotoxigenic E. coli (ETEC) is the predominant cause of E. coli-mediated diarrhea in the developing world and is responsible for a significant portion of pediatric deaths. In this study, we determined the complete genomic sequence of E. coli H10407, a prototypical strain of enterotoxigenic E. coli, which reproducibly elicits diarrhea in human volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains, revealing that the chromosome is closely related to that of the nonpathogenic commensal strain E. coli HS and to those of the laboratory strains E. coli K-12 and C. Furthermore, these analyses demonstrated that there were no chromosomally encoded factors unique to any sequenced ETEC strains. Comparison of the E. coli H10407 plasmids with those from several ETEC strains revealed that the plasmids had a mosaic structure but that several loci were conserved among ETEC strains. This study provides a genetic context for the vast amount of experimental and epidemiological data that have been published. Description: PUBLISHED 2010-01-01T00:00:00Z http://hdl.handle.net/2262/39201 Title: An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit. Author: MURPHY, PHILIP Abstract: OBJECTIVES: To report an outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit (ITU). METHODS: An outbreak of colonization with linezolid-resistant S. epidermidis affecting 16 patients in an ITU was investigated using PFGE. Environmental and staff screening was carried out as part of the investigation. Usage of linezolid in the hospital and in the ITU was reviewed. Resistant strains were screened for the presence of the G2576T mutation using PCR-RFLP genotyping. The interventions made to control the outbreak were restriction of linezolid prescription and specific infection control measures, including isolation of colonized patients and increased environmental cleaning. RESULTS: Linezolid-resistant S. epidermidis strains from the 16 colonized patients were genetically related. The same strain was also cultured from environmental samples in the ITU. An increase in linezolid usage in the hospital and in the ITU occurred in the 6 months prior to the emergence of the resistant strain. Infection control measures and restriction of linezolid prescription controlled the outbreak. All resistant isolates contained the G2576T mutation. CONCLUSIONS: An outbreak of colonization with linezolid-resistant S. epidermidis occurred in the ITU in our institution. The resistant strain colonized the environment and probably spread from patient to patient. The outbreak was associated with an increase in the linezolid usage in the ITU and in the institution as a whole. Restriction of linezolid usage and infection control measures were introduced to control the outbreak. The emergence of linezolid resistance in S. epidermidis has implications for the use of linezolid as a therapeutic agent. Description: PUBLISHED 2008-01-01T00:00:00Z