PhD defence

Semisynthetic Glycopeptide Antibiotics

• E. van Groesen

Date

Wednesday 12 October 2022

Time

15:00 - 15:45 hour

Address

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof. N.I. Martin

Summary:

The accelerated appearance of drug-resistant pathogens continues to present a growing threat to modern medicine’s capacity to fight infectious disease. A recent Lancet study estimates that in 2019 antimicrobial resistance (AMR) was directly responsible for a staggering 1.27 million deaths worldwide and further associated with an estimated 4.95 million deaths. Among the pathogens that contribute most to this global burden of AMR, drug resistant variants of the Gram-positive species S. aureus and S. pneumonia are responsible for a combined 0.5 million annual deaths. Historically, treatment of such Gram-positive infections has relied upon the glycopeptide family of antibiotics, typified by vancomycin, as a last line of defense. In recent years however, vancomycin-resistance has emerged highlighting the importance of developing next generation glycopeptides with enhanced antibacterial activities and improved safety profiles. In this thesis, a variety of semisynthetic glycopeptides were developed and assessed for their antimicrobial activity, using different strategies. The guanidino lipoglycopeptides (described in Chapter 2-3) have potent in vitro and in vivo activity against Gram-positive strains and have the potential to become the new best in class. The vancomyxins (Chapter 4) and the vancomycin-sideromycins (Chapter 5) take a different approach by targeting Gram-negative strains, which normally are not sensitive to glycopeptide antibiotics. Overall, this thesis describes diverse strategies to tack antimicrobial resistance to both Gram-positive and Gram-negative strains.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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