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Mechanisms of Adaptation to Deformylase Inhibitors

Zorzet, Anna, 1977- (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Dan Andersson
Andersson, Dan, Professor (thesis advisor)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Rainey, Paul, Professor (opponent)
Massey University
 (creator_code:org_t)
ISBN 9789155478285
Uppsala : Acta Universitatis Upsaliensis, 2010
English 68 s.
Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 571
  • Doctoral thesis (other academic)
Abstract Subject headings
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  • Antibiotic resistance is a growing problem on a global scale. Increasing numbers of bacteria resistant toward one or multiple antibiotics could return us to the high mortality rates for infectious diseases of the pre-antibiotic era. The need for development of new classes of antibiotics is great as is increased understanding of the mechanisms underlying the development of antibiotic resistance. We have investigated the emergence of resistance to peptide deformylase inhibitors, a new class of antibiotics that target bacterial protein synthesis. The fitness of resistant mutants as well as their propensity to acquire secondary compensatory mutations was assessed in order to gain some insight into the potential clinical risk of resistance development. Most of this work was done in the bacterium Salmonella typhimurium, due to the availability of excellent genetic tools to study these phenomena. In addition, we have studied the bacterium Staphylococcus aureus as peptide deformylase inhibitors have been shown to have the greatest effect on Gram-positive organisms. In the course of this work we also examined the mechanistic aspects of translation initiation. Using a cell-free in vitro translation system we studied the effects of various components on translation initiation. These results have been combined with results obtained from resistant and compensated bacterial strains in vivo to gain new insights into the mechanisms of translation initiation.

Subject headings

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Keyword

antibiotic resistance
compensatory evolution
compensatory mutations
protein synthesis
initiation factor 2
initiator tRNA
formylation
peptide deformylase inhibitors
Bacteriology
Bakteriologi
Mikrobiologi
Microbiology
Biokemi
Biochemistry
Geography
Geografi

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vet (subject category)
dok (subject category)

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