Genomic characterization of antimicrobial resistance mechanisms in Pseudomonas aeruginosa clinical isolates
1 juli 2020
UAntwerp - online - - - - -
Andreu Coello Pelegrin
Prof. H. Goossens and dr A. van Belkum
PhD defence Andreu Coello Pelegrin - Faculty of Medicine and Health Sciences
Pseudomonas aeruginosa is a rod-shaped, gram-negative Gammaproteobacteria common in healthcare-associated infections. It is responsible for a wide range of diseases from local and acute infections to systemic and chronic diseases, some of which can be life-threatening. P. aeruginosa has a “plastic” genome, meaning that its size can vary, and therefore encode a variable number and wide range of genes, including those encoding transporters, metabolic pathways, virulence and antimicrobial resistance genes.
This thesis has an introductory chapter, in which the antimicrobial resistance (AMR) crisis is placed in context and the main clinical aspects of this bacterial species are detailed (Clinical relevance, Host-pathogen interaction, AMR mechanisms, epidemiology and treatment of multi-drug resistant isolates). Additionally, it has a short section on the role of molecular diagnostic tools in infectious diseases. The introduction is followed by four chapters with experimental data.
The first one describes the epidemiology and carbapenem resistance mechanisms from P. aeruginosa in a large intensive care unit in Jakarta, Indonesia, revealing endemic carbapenemase producing strains, which are associated with prolonged ICU stay. Colonisation or infection of patients with carbapenem resistant P. aeruginosa is affecting survival.
The second chapter analyses the same setting to assess the impact of a multifaceted infection control intervention analysed at the microbial genomic level, documenting the usefulness of whole-genome sequencing (WGS) in combination with clinical data to evaluate the impact of an infection control intervention.
The third experimental chapter evaluates multiple whole-genome sequencing-based typing approaches for P. aeruginosa. cgMLST, wgMLST and cgSNP were found to provide the highest level of resolution allowing detailed epidemiological analysis of local outbreaks and international dissemination; MLVA is confirmed to be a suitable alternative for accurate typing of P. aeruginosa, useful in settings where the transition towards WGS is currently not feasible.
The fourth manuscript analyzes the phenotypic and genomic variability of serial peri-lung transplantation P. aeruginosa isolates from cystic fibrosis patients. It is observed that despite lung transplantation and associated clinical and therapeutic measures, all patients remained persistently colonized with similar strains, and that mild variations were observed at isolate level. The study concludes that using a combination of clinical and multi-omics approach could help to devise the appropriate treatment for the patients.
In conclusion, the thesis shows that WGS and downstream bioinformatics allow for detailed epidemiological analyses of collections of P. aeruginosa strains, providing new insights in their local and global dissemination.