Serratia marcescens: Outer membrane porins and comparative genomics
| dc.contributor.author | Diamandas, Alexander | |
| dc.contributor.examiningcommittee | Kumar, Ayush (Microbiology) Cardona, Silvia (Microbiology) Bay, Denice (Medical Microbiology) | en_US |
| dc.contributor.supervisor | Brassinga, Ann Karen (Microbiology) | en_US |
| dc.date.accessioned | 2020-01-09T15:54:26Z | |
| dc.date.available | 2020-01-09T15:54:26Z | |
| dc.date.issued | 2019-12-31 | en_US |
| dc.date.submitted | 2020-01-02T22:50:14Z | en |
| dc.degree.discipline | Microbiology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | The Gram negative bacterial species Serratia marcescens is an increasingly prevalent and dangerous cause of health care acquired infections. Its high inherent resistance to first line antimicrobials, paired with a very plastic genome and diverse plasmid compatibility make multi drug resistance a common challenge to treatment of S. marcescens infections. One such genetic change that can lead to drug resistance in this species is the loss of certain Outer Membrane Porins (OMP) that normally facilitate diffusion of antimicrobials, particularly β-lactam antibiotics. Previous research into other enterobacteriaceae species has indicated that these strains often exhibit altered virulence in host models. We used an existing library of S. marcescens Db11 OMP mutants to evaluate virulence in Caenorhabditis elegans and Galleria mellonella host models. We observed significant but not biologically relevant increases in virulence of the ΔompCΔompF and ΔompCΔompFΔphoE strains. Other porin genes were evaluated for expression in the mutant strain backgrounds in order to observe changes resulting from loss of ompC, ompF and phoE. A significant reduction of the lamB gene in all strains, and significantly increased expression of ompA and ompX in both double and triple deletion strains. This is the first evidence of ompA overexpression due to loss of ompC and ompF function. This study also sought to investigate the genomic properties of two clinical isolates, in order to establish their compatibility with existing genetic tools for the manipulation of OMP genes, for the purpose of studying the effects in different genetic backgrounds. Two strains of S. marcescens isolated from platelet concentrate, CBS11 and CBS12, had their genomes sequences prepared and analysed. The two strains were also evaluated for virulence in C. elegans, revealing CBS11 as significantly hyper virulent as compared to both CBS12 and Db11. The high homology of OMP genes in these strains and Db11 makes them excellent candidates for manipulation with existing tools designed for a Db11 background. | en_US |
| dc.description.note | February 2020 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34466 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Microbiology | en_US |
| dc.subject | Virulence | en_US |
| dc.subject | Bacteria | en_US |
| dc.title | Serratia marcescens: Outer membrane porins and comparative genomics | en_US |
| dc.type | master thesis | en_US |