Mechanisms of Reduced Vancomycin Susceptibility in Staphylococcus aureus
| Autor: | Meng Wei Yang, 楊孟薇 |
|---|---|
| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 Due to wide use of antibiotics, many drug resistant S. aureus are isolated. Previous studies demonstrated that dysfunction of accessory gene regulator (agr) is associated with reduced vancomycin susceptibility (RVS). However, the relationship between RVS and agr dysfuction is still controversial. This study investigated that whether agr dysfunction contributes directly or indirectly to RVS. We found that restoration of agr function in the clinical strain 2482, which has a mutation in agrC and shows RVS phenotype, cannot restore vancomycin susceptibility of strain 2482. Moreover, M253 and M945 which are transposon insertional mutants with the mutations in agr locus, did not show RVS phenotypes, indicating that agr dysfunction dose not contributes directly to RVS. In addition, the study generated two agr deletion mutants HG001ΔagrA and 29213ΔagrA and examined whether agr dysfunction enhances bacterial survival under drug selection pressure. The results showed that agr dysfunction did not provide a niche for bacterial survive during vancomycin treatment. Additionally, this study analyzed the sequences of the entire agr locus in 11 VISA and 10 hVISA clinical strains and found that the occurrence of a point mutation leading to replacement of serine with arginine at position 6 in AgrC of all tested strains. The relationship between sequence type (ST) and RVS was also investigated in this study. The results demonstrated that ST-239 strains are more resistant to vancomycin treatment than the ST5 and ST59 strains. Furthermore, we found that most strains showing RVS phenotype can be reversed to the phenotype of vancomycin susceptibility after drug removal, indicating that RVS results from environmental adaptation, not genetic evolution. In conclusion, the information obtained from the study leads to a better understanding on mechanisms of RVS in S. aureus. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|