This project will provide an exciting opportunity for an enthusiastic honours student to join the Lung Bacteria group at QIMR Berghofer Medical Research Institute. The student will work in the research area of Pseudomonas aeruginosa lung infection in cystic fibrosis (CF). In particular, the student will investigate antibiotic resistance mechanisms in P. aeruginosa, which causes the majority of mortality and morbidity in CF.
In vitro susceptibility testing is used routinely to determine if a bacterial strain is susceptible or resistant to an antibiotic; however, there is a lack of correlation between predicted in vitro susceptibility and clinical outcomes in the setting of chronic P. aeruginosa infection. Therefore, there is an urgent need to improve understanding of the underlying antibiotic resistance mechanisms in multi-drug resistant P. aeruginosa strains so that we can identify markers for better evidence-based decisions on antibiotic selection. Using whole genome sequencing we recently found that chromosomal mutations constitute the major mechanism of acquired antibiotic resistance in P. aeruginosa from the CF lungs.
In the proposed project the student will learn how to perform site-directed mutagenesis to determine the impact of mutational events on antibiotic resistance in P. aeruginosa. These comprise >50 mutations, including: a nucleotide substitution in the ampC-ampR intergenic region (-10 promoter of ampC) that could cause hyper-production of the AmpC cephalosporinase; a specific mutation in oprD (outer membrane porin) that could cause prevent uptake of carbapenems; missense or frameshift mutations within efflux pump regulators (including mexT, mexS, mexZ) that could affect susceptibility to antibiotics from different classes.
- Honours project or is flexible for a clinical student.