2026-09-18T17:48:44Zhttps://publikationen.uni-tuebingen.de/oai/requestoai:publikationen.uni-tuebingen.de:10900/1684612025-07-30T01:05:00Zcom_10900_42126col_10900_42133
Publikationssystem UB Tuebingen
advisor
Peschel, Andreas (Prof. Dr.)
author
Krusche, Janes
2025-07-29T09:48:57Z
2027-07-10
http://hdl.handle.net/10900/168461
Dissertation gesperrt bis zum 10.07.2027!
Staphylococcus aureus is one of the most prevalent bacterial pathogens worldwide. While many antibiotics were successfully used to treat infections in the past, antibiotic resistance rates are rising, and new approaches are required. Among these approaches, viruses of bacteria, called bacteriophages, are especially interesting. Since phages are highly selective for their host bacteria, they exert minimal pressure on the overall microbiota. However, the exact interactions, and the cause for this selectivity, remained unclear. It was known that most S. aureus phages bind to the cell wall bound wall teichoic acid (WTA) glycopolymer, which, in S. aureus, consists of ribitol-phosphate (RboP) repeats with different glycosylations, but the exact WTA-glycosylation dependent binding pattern of most phages was unknown. In this work, we elucidated the binding pattern of S. aureus phages by combining computational identification and clustering of phage receptor-binding proteins (RBPs) and analysis of binding to S. aureus WTA mutant panels via fluorescently labelled RBPs. This way, we discovered that S. aureus phage RBPs cluster in distinct groups, each with its own distinct binding pattern that matches the binding behavior of the intact phage. Additionally, we discovered that many S. aureus phages carry two separate RBPs, both binding to the WTA of their host. Next, we discovered that S. aureus can modulate its WTA glycosylation pattern via autoinducer peptides (AIPs) of the quorum-sensing agr system. This process can also be exploited by other staphylococci by using alternative AIPs with inhibitory or stimulatory activity, thus altering the metabolism and WTA composition of S. aureus. Lastly, we discovered that Staphylococcus epidermidis E73 uses a novel glycosyltransferase, TarM(Se), to attach glucose to the RboP-WTA instead of the N-acetylglucosamine modification conferred by S. aureus TarM. Our study is the first description of RboP-WTA decorated with glucose, and the structure and function of TarM(Se) was elucidated. Overall, we were able to uncover many aspects of the phage-host interaction in S. aureus, but further research is necessary to better understand and optimize the treatment of S. aureus with bacteriophages.
en
ubt-podno
Molecular Interactions Governing Phage Specificity in Staphylococcus aureus
PhDThesis
URL
https://publikationen.uni-tuebingen.de/xmlui/bitstream/10900/168461/2/KruscheJanes_Dissertation.pdf
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application/pdf
KruscheJanes_Dissertation.pdf
URL
https://publikationen.uni-tuebingen.de/xmlui/bitstream/10900/168461/3/KruscheJanes_Dissertation.pdf.txt
File
MD5
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KruscheJanes_Dissertation.pdf.txt