• Director: Dr. A.-L. Banuls (IRD) and Prof. Dang Duc Anh (NIHE)
• Coordinator USTH: Dr. Nguyen Quang Huy
• Location: The campus of NIHE and USTH

1. History, Objectives and Research results

This LMI (Laboratoire Mixte International) was set up and funded in 2016 by different Vietnamese and French partners, as well as partners from Laos, Cambodia and UK.

Antibiotic resistance poses real problems in human and animal health worldwide, especially with the emergence of more and more resistant strains. South East Asia is the epicenter of many infectious diseases and also a major source of resistant and multidrug-resistant bacteria. In this alarming context, controlling their emergence and transmission has become a priority for all public health systems in this region.

Antibiotic resistance is probably the most common form of resistance and probably one of the most complex because of the particular characteristics of the bacterial biology. Antibacterial resistance may be encoded by one or more genes. It can occur by mutation and / or selection in a patient, following treatment (secondary resistance) or transmitted between patients (primary resistance). It may be vertically transmitted from one cell to another, by bacterial division or horizontally via a variety of mechanisms (between same species bacteria, or of different species). Besides these complex mechanisms at the cellular level, the spread of resistance occurs between diverse ecosystems characterized by different selection pressures (hospital and community settings, agricultural and urban environments ...). The knowledge of these evolutionary mechanisms is essential for the development of appropriate and efficient strategies to fight and control drug resistance.

Objectives:

The purpose of the International Joint Laboratory DRISA is to get an overview of the mechanisms of drug resistance emergence and its transmission at different spatial and temporal scales. This will be achieved by developing complementary approaches involving (1) observational studies in hospital and community settings and in different environments, (2) experimental research, and (3) mathematical modeling.

Observational studies collect data that are unfortunately still frequently lacking. They also contribute to the characterization of transmission within and between the main compartments. Experimental studies help understanding the molecular mechanisms of resistance and mathematical modeling allow global analyzes of the data obtained but also to guide their collection and the experimental approaches. The models are also used to explore and test hypotheses for which experimentation is impossible and to assist in the development of public health policies. In addition to research programs, the LMI is strongly involved in both training and innovation.

Training is provided as part of the teachings at the University of Science and Technology of Hanoi (USTH) and by the supervision of PhD and master students. Specific trainings are also opened to professionals. Innovation aim to develop new technologies and diagnostic tools, as well as to study new antibacterial molecules.

2. Partnership 

• Vietnamese partners 

1. National Institute of Hygiene and Epidemiology (NIHE), Hanoi
2. Oxford University Clinical Research Unit (OUCRU), Hanoi

• International partners 

1. UMR MIVEGEC (IRD, CNRS, Montpellier University), France
2. Pasteur Institute Cambodia (IPC), Phnom Penh, Cambodia
3. Infectious Diseases Center of Laos-Christophe Mérieux (CILM), Vientiane, Laos
4. Laboratory of Emerging Pathogens (LPE), (Fondation Mérieux), Lyon, France

3. Funding sources

IRD, CNRS, USTH, USTH consortium, French Embassy, Fondation Mérieux, Institut Pasteur du Cambodge, NIHE, ADB.

4. Equipment

 

No	Equipment	Location
1	L2 with full equipment	USTH
2	Printer	USTH
3	Autoclave	USTH
4	DNA and Protein Gel Electrophoresis	USTH
5	Incubator	USTH
6	Sample storage fridge	USTH
7	Freezer -20°c	USTH
8	PCR machine	NIHE
9	Scanner for microarray	NIHE
10	Hybridization oven	NIHE
11	Incubator CO2	NIHE
12	Centrifuge	NIHE

 

5. Ongoing research activities developed with USTH lecturers

5.1. Observational studies

5.1.1. One health projects

1. Metabolic adaptation of plants on multi-contaminated soils with metals and antibiotics: consequences on rhizosphere bacterial communities and the selection of MultiDrug Resistant populations.

Lecturers involved: Dr Pham Hoang Nam (PI), Dr Nguyen Thi Kieu Oanh, Dr Nguyen Quang Huy, Dr Nguyen Thy Ngoc, Dr Nguyen Thi Thu Hang.

Other researchers involved : Assoc. Pr. LE Mai Huong, INPC, VAST; Pr. Marie-Geneviève Dijoux-Franca & Dr. Sylvie Nazaret (UMR 5557 CNRS Lyon, France); Dr. Anne-Laure Bañuls, (MIVEGEC, LMI DRISA, IRD Montpellier, France) ; Dr Tran Hoang Huy (NIHE, LMI DRISA,Vietnam).

2. Ecology and evolution of antibiotic resistance in Vietnam towards a “one health” approach (humans, animals and environment)

Lecturers involved: Dr Pham Hoang Nam, Dr Nguyen Thi Kieu Oanh, Dr Nguyen Quang Huy

Other researchers involved: Dr Thanh-Son Tran (Quy Nhon University, Vietnam);  Dr Tran Hoang Huy (NIHE, LMI DRISA,Vietnam), Pr. Marie-Geneviève Dijoux-Franca (UMR 5557 CNRS Lyon, France); Dr Jean Christophe Auguet (UMR MARBEC, France); Dr. Anne-Laure Bañuls (MIVEGEC, LMI DRISA, IRD Montpellier, France); Pr Sylvain Godreuil (CHU Arnaud de Villeneuve, LMI DRISA, MIVEGEC, Montpellier).

5.1.2. Molecular epidemiology and evolution of drug resistance within Mycobacterium tuberculosis in South East Asia (Vietnam, Cambodge, Laos).

Lecturers involved: Dr Nguyen Quang Huy

External researchers involved: Dr Nguyen Thi Van Anh (NIHE, LMI DRISA, Vietnam), Dr Silaphet Somphavong (CILM, LMI DRISA, Laos), Dr Sokleaph Cheng (IPC, LMI DRISA, Cambodge), Dr Mallorie Hide (IPC, LMI DRISA, Cambodge), Dr Alexandra Kerleguer (IPC, LMI. DRISA, Cambodge), Dr. Anne-Laure Bañuls (MIVEGEC, LMI DRISA, IRD Montpellier, France); Pr Sylvain Godreuil (CHU Arnaud de Villeneuve, LMI DRISA, MIVEGEC, Montpellier).

5.2. Experimental studies

5.2.1. SAPAA project: In vitro and in silico screening of natural compounds against main drug resistant bacteria in Vietnam: Towards the identification of new targets and mechanisms of action.

Lecturers involved: all the lecturers of the PMAB department (coPI: Dr Nguyen Thi Kieu Oanh)

External researchers involved: Pr Michel Lebrun (IRD, LMI RICE), Dr Anne-Laure Bañuls (coPI, MIVEGEC, LMI DRISA, IRD, Montpellier), Dr Baptiste Vergnes (MIVEGEC, LMI DRISA, IRD, Montpellier), Pr Marie-Geneviève Dijoux-Franca (UBCL, Lyon), Dr Duong Thi Ly Huong (SMP-VNU, Vietnam), Dr Nguyen Huy Hoang (NIHE, LMI DRISA, Vietnam), INPC researchers (Laboratory of Bioassay, INPC, Vietnam).

5.2.2. Pyrazinamide resistance in Mycobacterium tuberculosis isolates from Vietnam : improving resistance diagnosis and evaluation of the fitness cost of resistance-associated mutations

Lecturers involved: Dr Nguyen Quang Huy (PI)

External researchers involved: Khanh Linh Tran (USTH student), Dr Nguyen Thi Van Anh (NIHE, LMI DRISA, NIHE, Vietnam), Dr Le Quang Hoa (HUST, Vietnam), Dr Baptiste Vergnes (MIVEGEC, LMI DRISA, IRD, Montpellier), Dr Anne-Laure Bañuls (MIVEGEC, LMI DRISA, IRD, Montpellier).

5.2.3. Evolution of drug resistance of Mycobacterium tuberculosis to Bedaquiline

Lecturers involved: Dr Nguyen Thi Van Anh, Dr Nguyen Quang Huy. 

External researchers involved : Dr Nguyen Thi Van Anh (PI, NIHE, LMI DRISA, NIHE, Vietnam), Dr Elodie Gazanion (MIVEGEC, Montpellier); Team of the mycobacteriology laboratory of National Lung Hospital of Hanoi.

5.3. Innovation

5.3.1. Development of a diagnostic kit for the drug resistance detection in Mycobacterium tuberculosis based on the microarray technology.

Lecturers involved: Dr Nguyen Quang Huy.

External researchers involved : Dr Nguyen Thi Van Anh (coPI, NIHE, LMI DRISA, NIHE, Vietnam), Nguyen Thi Ngoc Anh (PhD student, LMI DRISA, MIVEGEC, NIHE, Montpellier/Hanoi), Dr Véronique Le Berre (LISPB, Toulouse), the team of Biochip and Bionanotechnogy plateform (Genopole, Toulouse), Dr Silaphet Sompavong (CILM, LMI DRISA, Laos), Dr Sokleaph Cheng (IPC, LMI DRISA, Cambodia), Dr Alexandra Kerleguer (IPC, LMI DRISA, Cambodia), Dr Anne-Laure Bañuls (coPI, MIVGEC, LMI DRISA, Montpellier).

5.3.2. Development of alternatives to antibiotics.

            1. See SAPAA project above

            2. Development of specific antimicrobial peptides

Lecturers involved: Dr Nguyen Quang Huy.

External researchers involved : Dr Nguyen Thi Van Anh (NIHE, LMI DRISA,Vietnam), Dr Dorothée Misse (PI, MIVEGEC, LMI DRISA, IRD, Montpellier), Dr Mallorie Hide (MIVEGEC, LMI DRISA, IPC, Cambodia), Dr Silaphet Sompavong (CILM, LMI DRISA, Laos), Dr Sokleaph Cheng (IPC, LMI DRISA, Cambodia), Dr Alexandra Kerleguer (IPC, LMI DRISA, Cambodia).

 

6. People involved in the LMI DRISA activities

 

No	Full name	Position	University/Institute	Remark
Vietnamese members
1	Nguyen Quang Huy	Lecturer/coordinator USTH	USTH
2	Pham Hoang Nam	Lecturer	USTH
3	Nguyen Thi Van Anh	Lecturer	USTH
4	Nguyen Thi Kieu Oanh	Lecturer	USTH
5	Nguyen Thy Ngoc	Lecturer	USTH
6	Dang Duc Anh	coDirector of LMI	NIHE
7	Nguyen Thi Van Anh	Researcher	NIHE
8	Vu Thi Thuong	Technician	NIHE
9	Tran Huy Hoang	Researcher	NIHE
10	Tran Thi Van Phuong	Engineer	NIHE
11	Nguyen Thi Ngoc Anh	PhD student	NIHE/MIVEGEC
12	Vu Tien Viet Dung	PhD student	OUCRU
13	Dr Le Viet Thanh	Post doctorate	OUCRU
International members
1	Silaphet Somphavong	PhD student	CILM, Laos
2	Phimpha Paboriboune	Scientific Director of CILM	CILM, Laos
3	Alun	Technician
4	Anne-Laure Bañuls	coDirector of LMI	IRD, Mivegec
5	Sokleaph Cheng	PhD student	IPC, Cambodia
6	Seiha Heng	Engineer	IPC Cambodia
7	Alexandra Kerleguer	MD	IPC Cambodia
8	Marc Choisy	Researcher	IRD, Mivegec
9	Mallorie Hide	Engineer	IRD, Mivegec
10	Samuel Alizon	Researcher	Mivegec
11	Dorothée Missé	Researcher	Mivegec
12	Ramsès Didjou-Demasse	Researcher	Mivegec
13	Sylvain Godreuil	Professor	Université Montpellier, Mivegec
14	Michel Lebrun	Director of PMAB department	USTH/IRD
15	Jean-Luc Berland	Engineer	LPE
16	Juliet Bryant	Scientific director of LPE	LPE
17	Florence Pradel	Manager	LPE
18	Rogier Van Doorn	Director of OUCRU	OUCRU

 

7. Main featured publications

 

No	Publications	Authors	Journal/Book	Year
1	Reduced turn-around time for Mycobacterium tuberculosis drug susceptibility testing with a proportional agar microplate assay	Nguyen VA, Nguyen HQ, Vu TT, Nguyen NA, Duong CM, Tran TH, Nguyen HV, Dang DA, Bañuls AL.	Clin Microbiol Infect. Dec;21(12):1084-92.	2015
2	Mycobacterium tuberculosis lineages and anti-tuberculosis drug resistance in reference hospitals across Viet Nam	Nguyen VAT, Bañuls AL, Tran THT, Pham KLT, Nguyen TS, Nguyen HV, Nguyen NLT, Dang DA, Marks GB, Choisy M.	BMC Microbiology. 16: 167	2016
3	High Nasal Carriage Rate of Staphylococcus aureus Containing Panton-Valentine Leukocidin- and EDIN-Encoding Genes in Community and Hospital Settings in Burkina Faso	Ouedraogo AS, Dunyach-Remy C, Kissou A, Sanou S, Poda A, Kyelem CG, Solassol J, Bañuls AL, Van De Perre P, Ouédraogo R, Jean-Pierre H, Lavigne JP, Godreuil S.	Front Microbiol. Sep 13;7:1406.	2016
4	Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis	Nguyen TV, Cao TB, Akkerman OW, Tiberi S, Vu DH, Alffenaar JW.	Expert Rev Clin Pharmacol. Aug;9(8):1025-37.	2016
5	Quadruple-first line drug resistance in Mycobacterium tuberculosis in Vietnam: What can we learn from genes?	Nguyen HQ, Nguyen NV, Contamin L, Tran THT, Vu TT, Nguyen HV, Nguyen NLT, Nguyen ST, Dang AD, Bañuls AL*, Nguyen TVA*.	Infect Genet Evol. Jun;50:55-61	2017
6	Molecular analysis of pyrazinamide resistance in Mycobacterium tuberculosis in Vietnam highlights the high rate of pyrazinamide resistance-associated mutations in clinical isolates	Nguyen QH, Contamin L, Hoa TTT, Hung NV, Lan NTN, Son NT, Nhung NV, Anh DD, Bañuls AL*, Nguyen TVA*.	Emerg Microbes Infect. Oct 11;6(10):e86.	2017
7	Bedaquiline Resistance: Its Emergence, Mechanism, and Prevention	Nguyen TVA, Anthony RM, Bañuls AL, Nguyen TVA, Vu DH, Alffenaar JC.	Clin Infect Dis. May 2;66(10):1625-1630.	2018
8	Antimicrobial resistance: the 70-year arms race between humans and bacteria	Bañuls AL, Nguyen TVA, Nguyen QH, Nguyen TNA, Tran HH, Godreuil S	In, Ecology and Evolution of Infectious Diseases in low-income countries: Pathogen Control and Public Health Management in Low-Income Countries. Roche B, Broutin H & Simard F (Eds.) Oxford University Press, New York. pp 77-90	2018
9	Insights into the processes that drive the evolution of drug resistance in Mycobacterium tuberculosis	Nguyen QH, Contamin L, Nguyen TVA*, Bañuls AL*	Evolutionary Applications;1–14	2018

 

8. Research outcomes or featured results have been achieved

- Achievement of the molecular study on drug resistance in Mycobacterium tuberculosis in Laos (one publication is submitted, PhD defense od Dr Silaphet Somphavong in December 2018) 9.5.

- Collaboration with Dr JC Auguet (CR CNRS, MARBEC, Montpellier) on the project “Unravelling the biogeographY of the Marine Pathobiome for HEalth and food management”. The project will be submitted on the 14th of September to the call “Key initiatives MUSE, Sea and Coast”. USTH lecturers will study the resistome in different ecosystems with different degree of humans activities (Aquaculture, fishermen villages, etc.)

- Type 2 funding of the project “Evaluation of synergic effects of metals and antibiotics in contaminated environments on the emergence of pathogenic (multi)drug resistant bacteria in the North of Vietnam” (PI: Dr Pham Hoang Nan) in the framework of the USTH Research Projects 2018 call.

-Achievement of the Laboratory level 2 for the SAPAA project in USTH.

- Achievement of the bachelor internship of Khanh Linh Tran in the framework of the Pyrazinamid project: Correlation between pyrazinamidase activities, pyrazinamide resistance in Mycobacterium tuberculosis and genetic variants of pncA gene.

- Achievement of the development of the diagnostic kit for detection of drug resistance in Mycobacterium tuberculosis based on microarray technology. Nguyen Thi Ngoc Anh will defense her PhD next November in France. A patent will be prepared.

- Production of a video on antibiotic resistance in collaboration with USTH / IRD / NIHE (in progress).

- Trainings : Thanks to French Embassy grants, Dr Nguyen Quang Huy in the framework of Bedaquiline project and Dr Nguyen Thy Ngoc in the framework of SAPAA project will be welcome for a training of one month in November on NGS data analysis in the UMR 1090 «Technologie Avancée pour le Génome et la Clinique », University Aix-Marseille.

- New arrivals: Dr Mallorie Hide is recently based at the Pasteur Institute in Cambodia for at least 2 years in the framework of the LMI DRISA. She will work on drug resistance in Mycobacterium tuberculosis and other bacteria bacteria in Cambodia and on the application of antimicrobial peptides as alternatives to antibiotics; Dr Ramsès Didjou-Demasse will arrive on 1st of October in MIVEGEC laboratory in Montpellier. He will work in the framework of LMI DRISA in Montpellier on the mathematical modeling of antibiotic resistance.

 

9. Gallery

copyright © IRD / François Carlet-Soulages, NOI Pictures