Regulation and function of resistance-nodulation-division efflux pumps in Acinetobacter baumannii ATCC17978 VU
| dc.contributor.author | Kornelsen, Vanessa | |
| dc.contributor.examiningcommittee | Court, Deborah (Microbiology) | |
| dc.contributor.examiningcommittee | Hausner, Georg (Microbiology) | |
| dc.contributor.examiningcommittee | Chelikani, Prashen (Oral Biology) | |
| dc.contributor.examiningcommittee | Stavrinides, John (University of Regina) | |
| dc.contributor.supervisor | Kumar, Ayush | |
| dc.date.accessioned | 2024-08-22T15:09:33Z | |
| dc.date.available | 2024-08-22T15:09:33Z | |
| dc.date.issued | 2024-08-13 | |
| dc.date.submitted | 2024-08-13T15:27:47Z | en_US |
| dc.degree.discipline | Microbiology | |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | |
| dc.description.abstract | The loss of effective therapeutic options due to the increase instances of antimicrobial resistant bacterial infections is of great concern to the World Health Organization (WHO). The WHO released a list to prioritize efforts in fighting this problem and placed carbapenem-resistant Acinetobacter baumannii as the top priority in need of development of new therapeutic options. A. baumannii is a Gram-negative opportunistic pathogen that can survive within clinical environments. A lot is known about the ability of this species to resist and tolerate the effects of antimicrobials. It possesses three efflux pumps of the resistance-nodulation-division (RND) efflux family, AdeAB(C), AdeFGH, and AdeIJK, that when overexpressed are responsible for reducing the susceptibility of A. baumannii to several antibiotic classes. These RND efflux pumps, and AdeFGH in particular, were the focus of my study. In this study I have investigated regulation and physiological function of AdeFGH, which is the least well studied RND efflux pump of the three. I have shown that AdeFGH expression has profound effects on the motility and biofilm formation of A. baumannii and that this is most likely due to increased efflux of acyl homoserine lactones. The effect of AdeFGH on motility and biofilm formation appears to be AdeL-independent. Interestingly, the overexpression of AdeL led to increased virulence in Galleria mellonella. I have discovered that the expression of adeFGH is induced by nitrosative stress and regulated by not only its cognate regulator, AdeL, but also by the global regulator, CsrA. I have investigated the role of CsrA in the physiology of A. baumannii via transcriptomics and phenotypic microarray. Additional investigations into AdeIJK showed it was crucial for A. baumannii virulence in G. mellonella and increased expression lead to increased tolerance to osmotic stress. All of this combined furthers our understanding of A. baumannii physiology and identifies several new potential therapeutic targets. | |
| dc.description.note | October 2024 | |
| dc.identifier.uri | http://hdl.handle.net/1993/38407 | |
| dc.language.iso | eng | |
| dc.rights | open access | en_US |
| dc.subject | Antimicrobial resistance | |
| dc.subject | bacterial stress response | |
| dc.title | Regulation and function of resistance-nodulation-division efflux pumps in Acinetobacter baumannii ATCC17978 VU | |
| dc.type | doctoral thesis | en_US |
| local.subject.manitoba | no |