Molecular Mechanisms of Antibiotic Resistance in - RePub

160 Pages·2004·4.23 MB·English

Molecular Mechanisms of Antibiotic
Resistance in Helicobacter pylori

Monique M. Gerrits
Financially support for this thesis was kindly given by:
Department of Gastroenterology and Hepatology, Erasmus MC
Section Experimental Gastroenterology of the Nederlandse Vereniging voor Gastroenterologie
Dr. J. Groenink
Janssen-Cilag B.V.
Roche diagnostics Nederland B.V.

ISBN: 90-9018512-7
Printed by: Optima
Cover illustration: Triple therapy, based on Pariet (Janssen-Cilag), Flagyl (Aventis
Pharma BV) and Amoxicillin
Cover design: Jasper Groenink

 M.M. Gerrits, The Netherlands, 2004. All rights reserved. No part of this thesis may be
reproduced or transmitted in any form or by any means, without permission of the author.
Molecular Mechanisms of Antibiotic
Resistance in Helicobacter pylori

Moleculaire mechanismen van antibioticum
resistentie in Helicobacter pylori

PROEFSCHRIFT

ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de Rector Magnificus
Prof.dr. S.W.J. Lamberts
en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op
donderdag 2 december 2004 om 13.30 uur
door

Monique Maria Gerrits

geboren te Zevenaar
Promotiecommissie

Promotor: Prof.dr. E.J. Kuipers

Overige leden: Prof.dr. M. Kist
Prof.dr. H.A. Büller
Prof.dr. H.A. Verbrugh

Copromotoren: Dr. J.G. Kusters
Dr. A.H.M. van Vliet
Aan Martin en Truus

CONTENTS

Chapter 1 Introduction, aims and outline of this thesis 9

Chapter 2 Antibiotic resistance in Helicobacter pylori: clinical 17
implications and molecular mechanisms

Chapter 3 16S rRNA mutation-mediated tetracycline resistance 47
in Helicobacter pylori

Chapter 4 Effects of 16S rRNA gene mutations on tetracycline 59
resistance in Helicobacter pylori

Chapter 5 Detection of high-level tetracycline resistance in clinical 65
isolates of Helicobacter pylori using PCR-RFLP

Chapter 6 Rapid detection of 16S rRNA gene mutations in 75
Helicobacter pylori associated with resistance to
tetracycline by real-time PCR

Chapter 7 The role of the rdxA and frxA genes in oxygen-dependent 87
metronidazole resistance of Helicobacter pylori

Chapter 8 Stable amoxicillin resistance in Helicobacter pylori 101

Chapter 9 Alterations in penicillin-binding protein 1A confer 105
resistance to β-lactam antibiotics in Helicobacter pylori.

Chapter 10 Mutational changes in the penicillin-binding protein 1A 115
gene mediate amoxicillin resistance in Helicobacter pylori

Chapter 11 Summary and concluding remarks 129

Samenvatting en conclusies 139
Dankwoord 149
Curriculum vitae 151
List of publications and conferences 153

1
CHAPTER

Introduction, aims and
outline of this thesis

M.M. Gerrits

Department of Gastroenterology and Hepatology, Erasmus MC - University Medical
Center, Rotterdam, The Netherlands.