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Browsing by Author "Mehaffy, Martha Carolina, author"

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    Proteomic and biological diversity of closely related clinical isolates of Mycobacterium tuberculosis
    (Colorado State University. Libraries, 2009) Mehaffy, Martha Carolina, author; Dobos, Karen, advisor
    Recent studies have indicated that some Mycobacterium tuberculosis {Mtb) strains may be more easily transmitted and successful in causing disease. While this phenotypic diversity exits and is well documented, protein variation between Mtb strains appears to be small. Historically, the analysis of virulence determinants in Mtb has focused on the comparison of virulent to avirulent Mtb strains as well as on the comparison of single gene knock-out mutants to Mtb reference strains. Biological and biochemical comparison of Mtb clinical isolates with different degrees of virulence, although more complex than those described above, might provide additional information regarding the natural phenotypic variability that exists in Mtb. The focus of this study was to determine if a group of closely related clinical isolates of Mtb (BE, C28 and H6) as well as the more distantly related Mtb CDC 1551 present differences in both, virulence in the guinea pig model of TB infection and in the protein expression profiles of secreted and cytosolic fractions. The three closely related Mtb isolates comprise the S75 group, which has been reported to be very successful in causing disease. In contrast, Mtb CDC 1551, although reported to be highly transmissible, is associated with only a few number of active TB cases. To test the hypothesis that closely related Mtb strains would have similar virulence between each other, but higher virulence when compared to Mtb CDC 1551, guinea pigs were infected with each Mtb strain and time-to-death analysis was performed. Proteomes of secreted and cytosolic fractions of these strains were also analyzed and compared by 2D-GE and isobaric tag labeling (iTRAQ) followed by tandem mass spectrometry in order to test whether protein levels of these strains would present statistically significant differences when compared to each other and when compared to Mtb CDC1551.