1. Full name: Tran Dieu Linh                                                       2. Sex: Female

3. Date of birth: 08 Aug 1982                                                     4. Place of birth: Hanoi

5. Admission decision number: Decision No. 4374/QD-KHTN-CTSV dated on 03/12/2012 by Rector of VNU University of Science.

6. Changes in academic process:

Revising thesis title, supervisors: Decision No. 5678/QD-DHKHTN dated on 19/12/2014 by Rector of VNU University of Science

Extension decision number 741/QD-DHKHTN dated on 31/5/2016 and 1034/QD-DHKHTN dated on 25/4/2017 by Rector of VNU University of Science

7. Official thesis title: Molecular characterization of some carbapenem-resistant Gram-negative bacteria isolated from patients in Vietduc hospital and 108 Military Central hospital.

8. Major: Microbiology                                                               9. Code: 62 42 01 07

10. Supervisors: Prof.Dr. Dang Duc Anh and Prof.Dr. Pham Van Ty       

11. Summary of the new findings of the thesis

The study detected different carbapenemase-coding genes and their variants in carbapenem-resistant E. coli, K. pneumoniae, and A. baumannii isolated in Vietduc hospital and 108 Military Central hospital.

431/622 strains (accounting for 69.3%) carry at least one gene coding for group A, B and D carbapenemase;

blaOXA-23 is the most common gene but only presented in A. baumannii wheares blaNDM-1 gene spread in all 3 studied bacteria;

First report of variants of carbapenemase-coding genes in Vietnam: blaNDM-6, blaNDM-9, blaOXA-181;

Above 90% of bacteria strains carrying carbapenemase-coding genes can produce carbapenemase enzymes;

The study results revealded some molecular characterizations of E. coli, K. pneumoniae, and A. baumannii isolates carrying carbapenemase-coding genes in the 2 hospitals.

High similarity in genotype of bacteria strains carrying carbapenemase-coding genes isolated in the same department, in different departments and in different collection years;

Presence of bacteria clonal lineages which are circulating and causing pandemic in Asia region and over the world, in large hospitals in Hanoi including E. coli ST101, ST38; K. pneumoniae ST15, ST11, ST307 together with bacterial clonal lineages firstly reported including E. coli ST48, ST709, ST448; K. pneumoniae ST1, ST391;

The study identified some molecular characteristics of the bacteria carrying carbapenemase-coding genes isolated in the two hospitals

Group A, B and D carbapenemase genes locate in plasmid varying in sizes and types:  blaKPC-2 genes localizing on 55 kb plasmids, IncF group; blaNDM-1 gene localizing on plasmid ranging from 45 to 170 kb in size, IncF group; and blaOXA-48 gene localizing on a 60 kb plasmid, IncL/M group. These plasmids can be transferred between bacteria strains via in vitro conjugation at successful rate of 20%.

Structural models of mobile genetic elements harboring carbapenemase-coding genes are quite diverged in case of blaKPC-2 and blaNDM-1 genes but are the same in case of blaIMP-1, blaOXA-48 and blaOXA-23 genes. These structures are similar to those of regional countries, exposing the possibility of quick spread of resistant bacteria via recombinant phenomena and horizontal gene transfer.

New contributions:

The first systematic research in Vietnam using Whole Genome Sequence techniques to characterize molecular carbapenem resistant mechanism of several pathogenic Gram-negative bacteria isolated from clinical specimens via producing carbapenemase enzymes.  

Results revealed at a certain extent the relationship of genotypes, sequence types among carbapenem-resistant bacteria in this study as well as in the world, thereby providing useful information on the source and spread of Gram-negative carbapenem resistant bacteria at study sites. 

The first study and molecular characteristics of plasmids and mobile genetic elements carrying genes coding for carbapenemase.

12. Practical applicability, if any:

Study results provides important information on the most common carbapenem-resistant mechanism, carbapenemase production, at molecular level; the spread of carbapenem-resistant Gram-negative using such mechanism in Vietnam and relationship with carbapenem-resistant bacteria in the world, which serve as scientific basis to propose appropriate infection control measures in hospitals and contribute to reduce the burden and spreading risk of drug-resistant bacteria to the community.

This research is the first systematic study investigate deeply on molecular carbapenem-resistant mechanisms, aiming at solving current scientific problems.

13. Further research directions, if any

To continue investigating other carbapenem-resistant mechanisms of Gram-negative bacteria such as porin loss, efflux pump.

Investigating the comprehensive structure of plasmids carrying resistent genes and regulatory and expression of resistant genes in plasmids using Nanopore MinION.

Evaluating antimicrobial resistant burden in enviroment and community.

14. Thesis-related publications:

[1] Tran Dieu Linh, Nguyen Hoai Thu, Tran Nhu Duong, Tran Van Phuong, Pham Duy thai, Nguyen Hiep Le Yen, Dang Duc Anh, Dinh Duy Khang, Trinh Hong Son, Pham Van Ty, Nguyen Binh Minh, Tran Huy Hoang (2016), "Emergence of E. coli carrying blaKPC-2 gene isolated in Vietduc Hospital from 2010-2012", Vietnam Medical Journal 443(6), pp. 70-73.

[2] Nguyen Hoai Thu, Tran Dieu Linh, Nguyen Thi Tuyet Mai, Pham Duy Thai, Tran Van Phuong, Nguyen Hiep Le Yen, Tran Nhu Duong, Dang Duc Anh, Nguyen Binh Minh, Dinh Duy Khang, Pham Van Ty, Tran Huy Hoang (2016), "Epidemiological characterization of hospital-acquired infections due to KPC-producing carbapenem-resistant Enterobacteriaceae isolated from Hospitals in Hanoi", Vietnam Medical Journal 444(7), pp. 148-152.

[3] Nguyen Hoai Thu, Tran Dieu Linh, Nguyen Thi Tuyet Mai, Pham Duy Thai, Tran Van Phuong, Nguyen Hiep Le Yen, Tran Nhu Duong, Dang Duc Anh, Nguyen Binh Minh, Dinh Duy Khang, Pham Van Ty, Tran Huy Hoang (2016), "Research on Extended-b-lactamases (ESBLs) genes in carbapenem resistant Enterobacteriaceae strains carrying   blaKPC-2 isolated from hospitals", Journal of Preventive Medicine  26(7), pp. 27-33.

[4] Tran Dieu Linh, Nguyen Thi Kim Phuong, Pham Duy Thai, Nguyen Thanh Thuy, Dang Duc Anh, Tran Nhu Duong, Pham Van Ty, Phan Quoc Hoan, Le Van Hung, Tran Huy Hoang (2018), "The spread of Gram-negative bacteria carrying carbapenemase genes isolated in 108 Military Central Hospital between 2014 and 2015", Journal of Preventive Medicine  28(1), pp. 45-52.