Antibiotic is one of the most significant human discoveries that continues to save millions of lives daily. Thanks to antibiotics, many modern medical procedures such as surgeries, cancer treatment, and organ transplants are made possible. Unfortunately, bacteria have adopted different survival strategies to gain resistance to a variety of antibiotics. Today, we face one of the most serious global health threats: antibiotic resistance, which is estimated to cause nearly 1.3 million deaths in 2019 and 10 million deaths annually by 2050 if no appropriate action is taken.

Our research focuses on major AMR infections-pathogens of local and regional significance, including diarrhoea (Shigella spp, nontyphoidal Salmonella), bloodstream infections (K. pneumoniae, ExPEC), typhoid fever (S. Typhi*,* S. Paratyphi A), and nosocomial infections (A. baumannii, K. pneumoniae).

Hosted by the largest hospital for tropical diseases in southern Vietnam, serving a population of 45 million people, we are in a unique position to capture epidemiological changes and clinical pictures of bacterial infections and look deeply into the causative bacteria in molecular details. By integrating genomics and molecular techniques into surveillance and clinical research, we provide unprecedented insights into antimicrobial resistance mechanisms, evolutionary process, and transmission dynamics of AMR bacteria in different populations, settings and ecosystems. We can also link AMR and bacterial genotype with treatment outcomes to delineate the impact of AMR on human health. Our work has made significant contributions to revising international/local treatment guidelines, controlling hospital outbreaks and informing public health actions.

Understanding is only the beginning. We have leveraged the advances in molecular biological techniques in the fields of microbiome, gene editing, AMR fitness and horizontal gene transfer in view of preventing and limiting the emergence and spread of AMR bacteria. In the near future, researchers in our group aim to study the immunological responses and identify vaccine candidates and delivery modes for K. pneumoniae, a key driver of infection and antibiotic use in both community and hospital settings in Vietnam and beyond.

Our research program is motivated by several key research questions:

• How do we best use genomics to timely detect and monitor the transmission of AMR bacteria on a national, regional and international scale?
• What are the benefits of genomics and molecular techniques in clinical detection, monitoring and treatment of AMR infections?
• What are the main ecological reservoirs of AMR bacteria and their roles in the emergence and transmission of novel AMR bacterial pathogens? And how do we reduce the spread of AMR bacteria?
• What factors drive AMR bacteria’s evolution, and how do we harness molecular techniques to reverse/decelerate the evolutionary process?

Research agenda

Our research activities are shaped around our four key main research questions.

How do we best use genomics to timely detect and monitor the transmission of AMR bacteria on a national, regional and international scale?

Antimicrobial resistance is a natural and unstoppable process which eventually leads to the emergence and spread of novel AMR variants. Similar to COVID-19, we know that AMR bacteria do not respect international borders; therefore, genomic surveillance is vital to rapidly identify and track the transmission of existing as well as novel AMR variants. Furthermore, since genomics has been internationally accepted as the gold standard in infectious disease surveillance, genomic data from one location can be easily integrated with additional local/global data to provide further contextualization for the epidemiology of AMR bacteria.

Our group have been working closely with many internal and external partners to conduct a range of genomics-based epidemiological and clinical surveillance of bacterial infections in Vietnam and Asia, including but not limited to pediatric diarrheal diseases, bloodstream infections and nosocomial infections. Our research findings have played an important role in depicting the changing landscape of drug-resistant bacterial infections in Vietnam and Asia and generated pivotal evidence to guide appropriate public health and hospital control measures. Building a research network as well as genome sequencing and analysis capacity within Vietnam and in Asia is a key strategy to timely detect new clinically and epidemiologically clones of local and regional significance.

What are the benefits of genomics and molecular techniques in clinical detection, monitoring and treatment of AMR infections?

The applications of whole genome sequence data in advancing clinical treatment and surveillance are one of our primary focuses. Hosted by the largest hospital for tropical diseases in South Vietnam, it is crucial that we have a good understanding and regular communications with clinicians, clinical microbiologists and infection control team to identify gaps and develop pragmatic solutions tailored to their needs.

Outbreak response: Our group have been working closely with frontline doctors, clinical microbiologists and the hospital infection control team to timely detect, confirm, control and prevent hospital outbreaks. Such coordination has allowed us to quickly control fatal hospital outbreaks caused by carbapenem- and colistin-resistant K. pneumoniae ST16. How we advocate and build this model across other hospital settings in Vietnam is a question of our focus in the coming years.

Diagnostics: We have successfully developed a simple, inexpensive molecular assay to rapidly detect key bacterial pathogens and their AMR genes from sputum and bronchoalveolar lavage samples. In a validation experiment with a small set of clinical samples, our assay showed higher sensitivity and specificity in comparison to the conventional culture method. Further validation and assessment of clinical utility are underway.

Another molecular assay that we have developed targets hypervirulent K. pneumoniae and its AMR genes, which can be adopted in clinical settings. Hypervirulent K. pneumoniae is a major cause of severe community-acquired infections in Vietnam, with infections can spread to other body sites causing liver abscess, pneumonia, bacteremia, meningitis, necrotizing fasciitis, endophthalmitis, and even sepsis. Therefore, rapid detection of this pathovariant can have major implications for clinical monitoring and management of patients.

What are the main ecological reservoirs of AMR bacteria and their roles in the emergence and transmission of novel AMR bacterial pathogens? And how do we reduce the spread of AMR bacteria?

The ecological reservoirs for the maintenance, emergence and transmission of AMR bacteria is a complex and understudied topic, particularly in LMICs. We have recently published a paper in Nature Microbiology highlighting the role of human commensal E. coli as an important reservoir for MDR plasmids in Shigella sonnei (Nat Microbiol. 2020 Feb; 5(2): 256–264.). This important finding motivates us to look deeper into the reservoirs and transmission dynamics of AMR bacteria at larger scales. We need to understand this complex picture of AMR emergence and transmission to design targeted public health control and preventive strategies.

What factors drive AMR bacteria’s evolution, and how do we harness molecular techniques to reverse/decelerate the evolutionary process?

Over the past two decades, we have learnt that the evolution of novel drug-resistant strains/clones is an ongoing and unstoppable process in which humans lag behind. Research in AMR evolution can narrow this gap and allow more time to develop appropriate public health control actions. For example, understanding the fitness effects of antibiotic resistance mutations/plasmids in the context of LMICs can help us to predict the evolutionary trajectories of AMR bacteria. Furthermore, if we can identify the key drivers for the emergence and spread of AMR bacteria, perhaps we can develop effective strategies to limit the spread of these organisms when they emerge and prevent their further re-emergence or decelerate and even reverse the evolutionary process.