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Cover Page

The handle http://hdl.handle.net/1887/66032 holds various files of this Leiden University

dissertation.

Author: Fleurbaaij, F.

Title: Novel applications of mass spectrometry-based proteomics in clinical microbiology

Issue Date: 2018-09-27

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Novel applicatioNs of

mass spectrometry-based

proteomics iN cliNical

microbiology

Frank Fleurbaaij

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ISBN: 978-94-930-1982-9

Cover and layout: Bregje Jaspers, ProefschriftOntwerp.nl Print: ProefschriftMaken, ProefschriftMaken.nl

©2018 Frank Fleurbaaij. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author or the journals holding the copyrights of the published manuscripts.

This work was supported financially supported by The Netherlands organisation of scientific research (NWO, ZonMW grant number 50-51700-98-142).

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Novel applicatioNs of

mass spectrometry-based

proteomics iN cliNical

microbiology

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op donderdag 27 september 2018

klokke 13:45 uur

door Frank Fleurbaaij geboren 9 november 1988

te Amsterdam

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Promotor

Prof. Dr. E. J. Kuijper Co-promotoren Dr. H. C. van Leeuwen Dr. P. J. Hensbergen

Leden promotiecommissie Prof. Dr. M. Wuhrer

Prof. Dr. A. van Belkum Prof. Dr. C. R. Jiminez Prof. Dr. J. T. van Dissel

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“Success does not consist in never making blunders but

in never making the same one a second time.”

- Henry Wheeler Shaw, 1874

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Table of contents

Chapter 1 Introduction

Chapter 2 Capillary-electrophoresis mass spectrometry for the detection of carbapenemases in (multi-)drug-resistant Gram-negative bacteria

Chapter 3 Direct detection of extended-spectrum beta-lactamases (CTX-M) from blood cultures by LC-MS/MS bottom-up proteomics

Chapter 4 Typing Pseudomonas aeruginosa isolates with ultrahigh resolution MALDI-FTICR mass spectrometry

Chapter 5 Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans

Chapter 6 Summary and discussion Chapter 7 Nederlandse samenvatting List of publications

Curriculum vitae

Acknowledgements

9 37

55 71 93

119 135 141 143 145

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