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Adaptation and evolution of drug-resistant Mycobacterium tuberculosis

Bergval, I.L.

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Citation for published version (APA):Bergval, I. L. (2013). Adaptation and evolution of drug-resistant Mycobacterium tuberculosis.

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Download date: 15 May 2020

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curriculumvitae

244 | CURRICULUM VITAE

Obviously, you’re not a golfer. - Jeffrey "The Dude" Lebowski

ABOUT | 245

About

Indra Bergval was born on October 31st 1975 in Delft, Netherlands. Already at a young

age she was fascinated by all creatures great and small, and after reading Midas

Dekkers and Charles Darwin she decided she would be a biologist one day.

She graduated from pre-university education in 1996. The following year she continued

her eduction with a study Biology at Leiden University, where she obtained a Master’s

degree in 2003. During her study she specialized in molecular biology, with an emphasis

on pathogenic micro-organisms. Her first (and main) internship, at the Institute of

Biology Leiden, was focused on a soil bacterium (Pseudomonas sp.) that produced an

antifungal compound against tomato root rot (Fusarium oxysporum f. sp. lycopersici.).

Interested to learn more about research in life sciences, she engaged in a second

internship at CLB/Sanquin Research, where she performed mutation analysis of Epstein-

Barr virus latent genes in HIV-1 infected homosexuals.

Her fascination with HIV reached beyond the laboratory bench; in 2003 she became a

volunteer with the AIDS-fonds, where she was involved with fundraising. In 2004,

together with three other volunteers from the AIDS-fonds, she organised [A]LIVE!, a

cultural benefit in the Stadsschouwburg in Amsterdam. The profits contributed to

making antiretroviral therapy freely available to HIV-infected individuals in a small

community in South Africa.

In 2004 she started working as a scientific researcher for KIT (Royal Tropical Institute)

Biomedical Research, where she performs molecular (micro)biological research on

antibiotic resistance in M. tuberculosis. Furthermore, she is involved in determining lines

of research focused on the detection and control of tuberculosis and writing project

proposals to fund these research lines. She has presented her research results in the

form of (peer-reviewed) scientific publications, posters, oral presentations and other

reports. In addition, she has supervised MSc students from various universities during

their internship at KIT Biomedical Research.

Within the Royal Tropical Institute she has also been involved with many non-scientific

activities, such as participating in an expert meeting on human remains at the

Tropenmuseum or in the process of rebranding the Institute.

She enjoys making science understandable for a broader audience and has undertaken

several activities to do so; she has, for instance, guided primary school students at the

IMC Weekendschool and she has taken part in several editions of the Klokhuis

Vragendag.

She lives together with Mark and their two children, Reza (m) and Miki (f).


Research projects

Project Title: Selection of appropriate treatment and infection control measures by

integrated high throughput genotyping and drug resistance determination of

Mycobacterium tuberculosis clinical isolates

Period: From 01/11/2010 till 31/10/2014

Client/Funding Agency: ZonMW/WOTRO

Position: Main applicant/scientific researcher

Researchers from KIT Biomedical Research have developed a molecular test that allows

the simultaneous detection of multiple mutations in the DNA of the TB bacteria. These

mutations provide information on antibiotic resistance and reveal which TB strain the

patient is infected with.

KIT Biomedical Research will, together with the RIVM, the AIGHD and MRC-Holland,

further develop this test. Additionally, the impact of such a test on the treatment

outcome of MDR-TB patients will be modelled, as testing would allow more

appropriated selection of antibiotic(s).

This project is funded by ZonMW and WOTRO and will be performed in collaboration

with TB reference laboratories in Bulgaria and Georgia.

Project Title: TB Adapt

Period: From 01/01/2008 till 31/12/2010

Client/Funding Agency: EU (6th Framework Programme)

Position: scientific researcher

TB Adapt is an EU FP6 STREP project studying how the various vaccination and

treatment programs have impacted on the TB epidemic and how the bacteria are

responding to these control measures. In this project were are working together with

many international partners, thereby ensuring that the subject is examined from a

broad spectrum of disciplines. KIT Biomedical Research is a major partner in the TB

Adapt project and we have commited to study the behaviour, perform identification and

characterisation, and determine the adaptability of different TB-strains that are

brought in by our different partners.

PUBLICATIONS | 247

Publications

PEER-REVIEWED LITERATURE :

Combined species identification, genotyping, and drug resistance detection of

Mycobacterium tuberculosis cultures by MLPA on a bead-based array.

Bergval I, Sengstake S, Brankova N, Levterova V, Abadía E, Tadumaze N, Bablishvili N,

Akhalaia M, Tuin K, Schuitema A, Panaiotov S, Bachiyska E, Kantardjiev T, de Zwaan R,

Schürch A, van Soolingen D, van 't Hoog A, Cobelens F, Aspindzelashvili R, Sola C, Klatser

P, Anthony R.

PLoS One. 2012;7(8):e43240.

Mycobacterium tuberculosis population structure determines the outcome of genetics-

based second-line drug resistance testing.

Streicher EM, Bergval I, Dheda K, Böttger EC, Gey van Pittius NC, Bosman M, Coetzee G,

Anthony RM, van Helden PD, Victor TC, Warren RM.

Antimicrob Agents Chemother. 2012 May;56(5):2420-7.

Pre-existing isoniazid resistance, but not the genotype of Mycobacterium tuberculosis

drives rifampicin resistance codon preference in vitro.

Bergval I, Kwok B, Schuitema A, Kremer K, van Soolingen D, Klatser P, Anthony R.

PLoS One. 2012;7(1):e29108.

Evaluation of a new molecular test for the identification of drug resistance in

Mycobacterium tuberculosis clinical isolates.

Bergval I, Sengstake S, Bachyiska E, Brankova N, Tankova K, Levterova V, Ivanova A,

Atanasova Y, Yordanova S, Abadia E, Sola C, Akhalia M, Aspindzelashvili R, van Soolingen

D, Anthony RM, Kantardjiev T, Panaiotov S.

Problems of Parasitic and Infectious Diseases. Volume 38, Issue 2, 2010, Pages 27-30.

Identification and genotyping of the etiological agent of tuberculous lymphadenitis in

Ethiopia.

Beyene D, Bergval I, Hailu E, Ashenafi S, Yamuah L, Aseffa A, Wiker HG, Engers H, Klatser

P, Sviland L.

J Infect Dev Ctries. 2009 Jul 1;3(6):412-9.

Resistant mutants of Mycobacterium tuberculosis selected in vitro do not reflect the in

vivo mechanism of isoniazid resistance.

Bergval IL, Schuitema AR, Klatser PR, Anthony RM.

J Antimicrob Chemother. 2009 Sep;64(3):515-23. doi: 10.1093/jac/dkp237


Development of multiplex assay for rapid characterization of Mycobacterium

tuberculosis.

Bergval IL, Vijzelaar RN, Dalla Costa ER, Schuitema AR, Oskam L, Kritski AL, Klatser PR,

Anthony RM.

J Clin Microbiol. 2008 Feb;46(2):689-99. Epub 2007 Dec 12.

Specific mutations in the Mycobacterium tuberculosis rpoB gene are associated with

increased dnaE2 expression.

Bergval IL, Klatser PR, Schuitema AR, Oskam L, Anthony RM.

FEMS Microbiol Lett. 2007 Oct;275(2):338-43. Epub 2007 Sep 14.

Acquisition of rifabutin resistance by a rifampicin resistant mutant of Mycobacterium

tuberculosis involves an unusual spectrum of mutations and elevated frequency.

Anthony RM, Schuitema AR, Bergval IL, Brown TJ, Oskam L, Klatser PR.

Ann Clin Microbiol Antimicrob. 2005 Jun 15;4:9.

OTHER MEDIA:

KIT: Resistente TBC snel opgespoord met genetische test.

Newsletter Amsterdam Economic Board (formerly Stichting KennisKring Amsterdam)

2012, volume 18, issue 3

Verbeterde screeningmethode voor tuberculose toont tegelijk drugresistentie aan.

KIT Update, trimonthly external newsletter Royal Tropical Institute, November 2012.:

Tuberculosebacterie gestresst door antibiotica-resistentie.

KIT Update, trimonthly external newsletter Royal Tropical Institute, November 2007

Interview on BNN Today, Radio 1 (Dutch national radiostation) about centennial

anniversary of Royal Tropical Institute, 11 March 2010.

PRESENTATIONS AND POSTERS | 249

Presentations and posters

POSTERS:

Accurate and efficient identification of drug resistance and local MDR cluster strains of

Mycobacterium tuberculosis using an adapted SNP-based multiplex LPA assay.

S. Sengstake, I. Bergval, A. Schuitema, K. Tuin, J. de Beer, N. Bablishvilli, N. Bzekalava,

N. Brankova, V. Levterova, E. Abadía, R. Aspindzelashvili, E. Bachiyska, C. Sola, S.

Panaiotov, D. van Soolingen, R. Anthony.

34th Annual Congress of the European Society of Mycobacteriology (ESM), Florence,

Italy, 30 June – 3 July 2013

Detection of multiple genetic markers on single MagPlex-TAG beads, combined data

processing and allele calling allows accurate characterization of Mycobacterium

tuberculosis isolates.

S. Sengstake, I. Bergval, K. Tuin, J. Nyagwange, A. Schuitema, R. Anthony.

Luminex xSAMPLES Benelux, Rotterdam, Netherlands, 2013

Screen my genome to reveal my secrets - Combined species identification, genotyping,

and drug resistance detection of Mycobacterium tuberculosis cultures by MLPA on a

bead-based array.

S. Sengstake, I. Bergval, N. Brankova, V. Levterova, E. Abadía, N. Tadumaze, N.

Bablishvili, M. Akhalaia, K Tuin, A Schuitema , S Panaiotov, E Bachiyska, T Kantardjiev, R

de Zwaan, A Schürch, D van Soolingen, A van ‘t Hoog, F Cobelens, R Aspindzelashvili, C

Sola, P Klatser, R. Anthony.

German Society for Hygiene and Microbiology, Hamburg, Germany, 2012

Identification of multiple targeted genetic markers in the Mycobacterium tuberculosis

genome by MLPA as a molecular research tool.

I. Bergval, A. Schuitema, B. Kwok, L. Streicher, K. Tuin, S. Sengstake, K. Kremer, D. van

Soolingen, R. Warren, P. Klatser, R. Anthony.

Tuberculosis 2012 – EMBO conference, Institut Pasteur, Paris, France, 11-15 September

2012

A multiplex assay for bacterial genotyping - Exploiting M. tuberculosis genetic diversity

and clonal architecture to explore the selection of successful bacterial lineages.

S. Sengstake, I. Bergval, N. Tadumaze, N. Bzekalava, M. Akhalaia, R. Aspindzelashvili, P.

Klatser, R. Anthony.

Tuberculosis 2012 – EMBO conference, Institut Pasteur, Paris, France, 11-15 September

2012


Characterisation of drug-resistant Mycobacterium tuberculosis strains from Bulgaria and

Georgia by bead-based Multiplex Ligation-dependent Probe Amplification.

S. Sengstake, I. Bergval, N. Brankova, V. Levterova, E. Abadía, M. Akhalaia, K. Tuin, A.

Schuitema, S. Panaiatov, E. Bachiyska, R. Aspindzelashvili, P. Klatser, C. Sola, R. Anthony.

22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID),

London, UK, 31 March – 3 April 2012

Development of a molecular assay to characterise Mycobacterium tuberculosis isolates:

Potential for scaling-up TB control.

I. Bergval, S. Sengstake, K. Tuin, E. Abadia, M. Akhalaia, A. Herrewegh, E. Bachyiska, R.

Aspindzelashvili, C. Sola, S. Panaiotov, F. Cobelens, D. van Soolingen, R. Anthony.

42nd Union World Conference on Lung Health, Lille, France, 26-30 October 2011

Bead-based Multiplex Characterisation of Mycobacterium Tuberculosis Clinical Isolates.

I. Bergval, S. Sengstake, K. Tuin, E. Abadia, A. Herrewegh, C. Sola, S. Panaiotov, P.

Klatser, R. Anthony.

Luminex Planet xMAP, Vienna, Austria, 2011

SNP typing of M. tuberculosis: one method, multiple applications.

I. Bergval, S. Sengstake, A. Schuitema, P. Klatser, R. Anthony.

31st Annual Congress of the European Society of Mycobacteriology, Bled, Slovenia, 4-7

July 2010

Acquisition of drug resistance in vitro suggests different adaptive pathways in

Mycobacterium tuberculosis genotypes.

I. Bergval, A. Schuitema, B. Kwok, P. Klatser, R. Anthony.

3rd FEMS Congress of European Microbiologists, Gothenburg, Sweden, June 28-July 2

2009

The accumulation of resistance mutations in Mycobacterium tuberculosis in vitro.

I. Bergval, A. Schuitema, P. Klatser, R. Anthony.

19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID),

Helsinki, Finland, 16-19 May 2009.

In vitro selected mutants of M. tuberculosis do not reflect the in vivo mechanism of

isoniazid resistance.



Barcelona, Spain, 19-22 April 2008


Preferred pathways to drug resistance in Mycobacterium tuberculosis strains elucidated

by MLPA

I. Bergval, A. Schuitema, L. Oskam, P. Klatser, R. Anthony.

ESCMID International symposium on Bacterial adaptation mechanisms: biofilms,

hypermutability and antibiotic resistance (BAMBHAR), Palma de Mallorca, Spain, 7-9

November 2007

Development of drug resistance in Mycobacterium tuberculosis.

I. Bergval, R. Anthony, A. Schuitema, L. Oskam, P. Klatser.

55th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Atlanta,

USA, 12-16 November 2006.

Specific mutations in the M. tuberculosis rpoB-gene are associated with increased SOS-

responses.


159th Meeting of the British Society for General Microbiology, York, UK, 11-14

September 2006.

Illumination with Light Emitting Diodes for fluorescent microscopic screening of

Mycobacterium tuberculosis.

R. Anthony, A. Kolk, I. Bergval, L. Oskam, P. Klatser.

159th Meeting of the British Society for General Microbiology, York, UK, 11-14

September 2006.

Specific mutations in the M. tuberculosis rpoB-gene are associated with increased SOS-

responses.


2nd FEMS Congress of European Microbiologists, Madrid, Spain, 4-8 July 2006.

Illumination with Light Emitting Diodes for fluorescent microscopic screening of


R. Anthony, A. Kolk, I. Bergval, L. Oskam, P. Klatser.

2nd FEMS Congress of European Microbiologists, Madrid, Spain, 4-8 July 2006.

Mutator strains may contribute to the acquisition of drug resistance in Mycobacterium

tuberculosis.

R. Anthony, A. Schuitema, I. Bergval, L. Oskam, P. Klatser.


Copenhagen, Denmark, 2-5 April 2005.


A hypermutator strain of Mycobacterium tuberculosis isolated after selection with

rifampicin.

I. Bergval, R. Anthony, A. Schuitema, T. Brown, L. Oskam, P. Klatser.

Joint Scientific Meeting on Infectious Diseases and Microbiology NVMM/VIZ/SBIMC-

BVIKM 2004, Royal Tropical Institute, Amsterdam, Netherlands, 18-19 November 2004.

ORAL PRESENTATIONS:

International scientific congresses and symposia

Evaluation of a bead-based M. tuberculosis-specific MLPA.


Invited speaker at workshop “Bead-based array technologies“, Robert Koch Institute,

Berlin, Germany, 7 November 2011

Validation of the Luminex system for the analysis of a Mycobacterium tuberculosis–

specific multiplexed SNP-detection method.

I. Bergval, S. Sengstake, A. Schuitema, P. Klatser, R. Anthony. Invited speaker at

Luminex Planet xMap 2010, Vienna, Austria, 20-21 October 2010

A high-throughput method for the simultaneous detection of drug resistance and

genotypic mutations in M. tuberculosis isolates.


20th European Congress of Clinical Microbiology and Infectious Diseases, Vienna,

Austria, 10-13 April 2010.

Preferred pathways to drug resistance in Mycobacterium tuberculosis strains elucidated

by MLPA

I. Bergval, A. Schuitema, L. Oskam, P. Klatser, R. Anthony..

ESCMID International symposium on Bacterial adaptation mechanisms: biofilms,

hypermutability and antibiotic resistance (BAMBHAR), Palma de Mallorca, Spain, 7-9

November 2007

Development of a low-cost and robust assay for the screening of multiple genetic loci in

M. tuberculosis.

I. Bergval, R. Anthony, E. Dalla Costa, A. Schuitema, L. Oskam, P. Klatser.

17th European Congress of Clinical Microbiology and Infectious Diseases, Munich,

Germany, 31 March-3 April 2007


Role of mutators in the evolution of bacterial pathogens

I. Bergval..

NvVM/NvMM Scientific Spring Meeting, Arnhem, Netherlands, 10-12 April 2006

Other

KIT Biomedical Research: An integrated approach to infectious diseases research.

I. Bergval (on behalf of KIT Biomedical Research).

Tropical Delights, Royal Tropical Institute, Amsterdam, Netherlands, 29 March 2012

No evidence for a genotype-dependent in vitro spectrum of resistance-conferring

mutations in Mycobacterium tuberculosis.

I. Bergval, B. Kwok, A. Schuitema, K. Kremer, P. Klatser, R. Anthony.

4th TB Adapt project meeting, Rio de Janeiro, Brazil, May 2010.

The influence of drug resistance and genotypic mutations on adaptive pathways of


I. Bergval, A. Schuitema, B. Kwok, P. Klatser, R. Anthony.

3rd TB Adapt project meeting, Capetown, South Africa, September 2009.

Wereldtuberculosedag 2009.

I. Bergval.

KIT Lunchlezing, Royal Tropical Institute, Amsterdam, Netherlands, 24 March 2009

In vitro selected mutants of M. tuberculosis do not reflect the in vivo mechanism of

isoniazid resistance.


2nd TB Adapt Project meeting, Oslo, Norway, April 2008

The emergence and evolution of drug-resistant tuberculosis.

I. Bergval, R. Anthony, A. Schuitema, L. Oskam.

KIT Lunchlezing, Royal Tropical Institute, Amsterdam, Netherlands, 25 November 2006

De wederopstanding van een dodelijke ziekte.

I. Bergval.

KIT Ledendag, Royal Tropical Institute, Amsterdam, Netherlands, 18 November 2006


Courses

Pathogen genomics and genomic epidemiology of infectious disease.

London School of Hygiene & Tropical Medicine, London, UK, 17-19 September 2012

2nd Symposium and Workshops on Molecular Microbiology of Infectious diseases.

Erasmus Medical Centre, Rotterdam, Netherlands, 19-20 June 2008

Molecular basis of bacterial infection: basic and applied research approaches.

Wellcome Trust Advanced Courses, Wellcome Trust Genome Campus, Hinxton, UK, 11-

17 May 2008

Write it right.

NWO Talent Classes, NWO, The Hague, Netherlands, 25 October 2005

Creative thinking.

NWO Talent classes, NWO, The Hague, Netherlands, 20 September 2005

Awards & Grants

NWO grant for open access publication of article Combined species identification,

genotyping, and drug resistance detection of Mycobacterium tuberculosis cultures by MLPA

on a bead-based array, Bergval et al., PLoS One 2012;7(8):e43240.

Faculty of 1000 recommendation “of special significance in its field” for article

Combined species identification, genotyping, and drug resistance detection of

Mycobacterium tuberculosis cultures by MLPA on a bead-based array, Bergval et al., PLoS

One 2012;7(8):e43240.

Oral presentation A high-throughput method for the simultaneous detection of drug

resistance and genotypic mutations in M. tuberculosis isolates, Bergval et al. held at the

20th ECCMID was awarded by the Nederlandse Vereniging voor Medische Microbiologie.

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