Gewählte Publikation:
Waidacher, C.
Characterization of Mutations in Ribosomal Protein S10 and Their Responsibility in Tigecycline Resistance.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2019.
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Zarfel Gernot
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- Abstract:
- Human induced antibiotic resistances are spreading all over the world leading to a severe threat to global health. Bacteria are evolving even faster, the more antibiotics were used, leading to the consequence, that infections like pneumonia and diarrhea, become more dangerous, as the antibiotics become less effective. As support in severe infections, special antibiotics with impact on multidrug resistant bacteria are used for treatment. Tigecycline is a modern antibiotic used for this purpose. But with the increased use, bacteria are also evolving resistance against this antibiotic agent.
Although resistance against Tigecycline can be achieved through different ways, a mechanism of huge interest is the occurring of mutations in ribosomal proteins in Klebsiella pneumoniae and Streptococcus pneumoniae, responsible for resistance against tigecycline.
The aim of this study was the construction of mutations in the ribosomal protein S10 and the characterization of these mutations. Therefore, an Escherichia coli strain was used as model organism to insert the specific mutations. After transformation the mutant strains were analysed for their growing performance, in order to investigate the general fitness costs of the inserted mutation. Furthermore, antibiotic resistance testing was performed to investigate the impact on antibiotic susceptibility. At least investigations on ribosome assembly and translational processes were executed via polysome profiling, as well as via RT q – PCR.
The constructed mutants reveal various results concerning the different investigations, involving slight to severe growing defects. In the resistance testing a higher resistance in some mutant strains was identified as well as a higher susceptibility. Aside from that mutant strains revealed defects in the assembly during ribosome biogenesis and during translation processes.