University of Groningen Breaking walls: combined peptidic activities against Gram-negative human pathogens Li, Qian

University of Groningen

Breaking walls: combined peptidic activities against Gram-negative human pathogens

Li, Qian

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2019

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Li, Q. (2019). Breaking walls: combined peptidic activities against Gram-negative human pathogens.

University of Groningen.

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Breaking walls:

combined peptidic activities

against Gram-negative

human pathogens

The work described in this thesis was carried out in Molecular Genetics Group of the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) of the University of Groningen, the Netherlands. The candidate was financially supported by the China Scholarship Council(CSC). Printing of this thesis was financially supported by the Graduate School of Science and Engi-neering and the University of Groningen.

Cover: Qian Li & Lovebird design. Layout: Lovebird design. www.lovebird-design.com

Printing: Eikon +

ISBN: 978-94-034-1343-3 (printed book) ISBN: 978-94-034-1342-6 (ebook)

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, without written permission of the author.

Breaking walls: combined peptidic

activities against Gram-negative

human pathogens

PhD thesis

to obtain the degree of PhD at the

University of Groningen

on the authority of the

Rector Magnificus prof. E. Sterken

and in accordance with

the decision by the College of Deans.

This thesis will be defended in public on

Monday 18 February 2019 at 9.00 hours

by

Qian Li

born on 10 April 1988

in Wuhan, China

Supervisor

Prof. O.P. Kuipers

Co-supervisor

Dr. M. Montalban -Lopez

Assessment Committee

Prof. A.J.M. Driessen

Prof. G.N. Moll

Prof. W. Bitter

To my family

Contents

Chapter 1 General Introduction

9

Chapter 2 Introducing a thioether ring in vasopressin by

nisBTC co-expression in Lactococcus lactis

49

Chapter 3 Increasing the antimicrobial activity of

ni-sin-based lantibiotics against Gram-negative

pathogens 79

Chapter 4 High synergistic antimicrobial activity against

Gram-negative bacteria of synthetic L- peptides

with vancomycin or nisin

107

Chapter 5 Efficient killing of Gram-negative pathogens by

highly synergistic action of GNP-D8 and

vanco-mycin or nisin: biological and pharmaceutical

characterization 123

Chapter 6 General Discussion

155

Summary

169

Samenvatting 173

Acknowledgments 179