Name & Department: Suhanya Prasad
Department of Medical Microbiology & Nanobiomedical Engineering
Public PhD Defence date: December 21, 2022
Doctoral Thesis title: Non-peptide mimics of antimicrobial peptides and their functionalized gold nanosystems to combat antibiotic resistance
Supervisor/s: Prof. dr hab. Robert Bucki
Dr hab. Krzysztof Fiedoruk
Reviewers: Prof. dr hab. Marek Droździk
Prof. dr hab. Marta Wróblewska
Dr hab. Marzena Wątek
Current affiliation: Charles University in Prague, Chech Republic
Plans for the Future: To continue my research in the area of microbial genomics; identifying the genomic determinants responsible for the spread of antimicrobial-resistant bacterial pathogens as well as finding alternative treatment solutions.
Abstract: Antimicrobial resistance (AMR) is a major concern in clinical settings, that has been related to the misuse and overuse use of antibiotics, as well as a crisis in the development of novel antimicrobial agents. Ceragenins (CSAs) are promising candidates for the founding of novel antibiotics. These non-peptide mimics of endogenous antimicrobial peptides (AMPs) are bactericidal and broad-spectrum antimicrobials with immunomodulatory properties. In addition, the antibacterial activity and biocompatibility of ceragenins may be improved by their attachment on the surface of nanomaterials, such as gold nanoparticles (AuNPs). The objective of this research was to study the antibacterial efficacy of ceragenins alone and in combination with peanut-shaped gold nanoparticles (AuP NP@CSA) against the leading etiological agents of middle ear infection ‒ Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In vitro experiments with induction of resistance to ceragenin CSA-13 and colistin in an emerging hospital pathogen ‒ Enterobacter hormaechei subsp. steigerwaltii (ST89) was used to investigate the potential mechanisms of resistance to these compounds. Notably, despite the common cationic nature of both agents, the prolonged exposure of E. hormaechei to CSA-13 induced only moderate level resistance to this ceragenin, compared to the high level of resistance to colistin observed in E. hormaechei upon exposure to this antibiotic. Furthermore, the whole-genome (WGS) and transcriptome (RNA-seq) analyses revealed that molecular mechanisms responsible for the high level of resistance to colistin developed by the studied E. hormaechei strain have no impact on its susceptibility to ceragenin CSA-13. Additionally, several novel mechanisms that directly or indirectly may contribute to the development of resistance to ceragenin CSA-13 and/or colistin in E. hormaechei have been identified.