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SUMMARY:Outsmarting Biofilms with Protease Triggered Peptide Prodrugs CH-6
 35
DTSTART:20260331T161500
DTEND:20260331T171500
DTSTAMP:20260501T102450Z
UID:ec409d95141c21c25b14222dd46fde0be2c141a721e65865cc8712a1
CATEGORIES:Conferences - Seminars
DESCRIPTION:Clarissa Melo Czekster\nAbstract : \nUp to 80% of bacterial c
 ells live in biofilms\, and over 80% of human microbial infections involve
  biofilm‑associated pathogens\, which are often highly resistant to anti
 biotics. Pseudomonas aeruginosa is a key model for studying chronic biof
 ilm infections due to its remarkable ability to persist for months or year
 s in nutrient‑poor environments. Extracellular proteases and peptidases 
 play central roles in these communities by generating nutrient pools\, dri
 ving structural remodelling\, enabling dispersal\, and detoxifying the env
 ironment. Many of these enzymes are produced as self-inhibited zymogens th
 at require processing to become active.\nBy dissecting the molecular mecha
 nisms of protease self‑inhibition\, we developed highly selective\, tigh
 t‑binding inhibitors and chemical probes that target both pre‑formed a
 nd newly forming biofilms. Building on this mechanistic understanding\, we
  mapped substrate preferences of key P. aeruginosa proteases and repurpo
 sed them as biofilm‑specific activators for an antimicrobial peptide pro
 drug. Although smart‑release antimicrobial strategies exist\, none harne
 ss the abundant\, biofilm‑specific proteases that dominate chronic infec
 tions\, and many rely instead on host enzymes which might not always be pr
 esent. Our protease‑activated peptide prodrug displays a low resistance 
 profile\, generating unique resistance mutations not observed in wild‑ty
 pe strains. Ongoing work is evaluating the fitness of these mutants and ex
 ploring synergistic combination strategies.\n\nBiography:\nClarissa Melo C
 zekster earned her PhD from Albert Einstein College of Medicine (2008-2012
 )\, studying mechanisms of enzymes in Mycobacterium tuberculosis\, and co
 mpleted postdoctoral training at Yale University (2012-2014) and at the Un
 iversity of St Andrews. In 2018\, she established her independent research
  group with a prestigious Wellcome trust Sir Henry Dale fellowship. Czekst
 er is currently a Reader in the School of Biology at the University of St 
 Andrews\, where she leads interdisciplinary research in enzymology\, struc
 tural biology\, microbiology and chemical biology. Her research focuses on
  developing novel antimicrobial and antibiofilm compounds\, engineering mi
 crobial natural product biosynthesis for biocatalysis\, and applying enzym
 e engineering to produce novel molecules. Additional areas include the syn
 thesis of unprecedented and isotopically labelled nucleosides and nucleoti
 des\, as well as peptide-based antimicrobials. Her group has established t
 echnologies enabling the production of antibiofilm peptides and nucleotide
 s from simple\, inexpensive precursors in a single step.\n\nWebsite:\nhttp
 s://czeksterlab.wp.st-andrews.ac.uk/ 
LOCATION:BS 150 https://plan.epfl.ch/?room==BS%20150
STATUS:CONFIRMED
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