Dr.
Pham Thanh Duy
Head of Molecular Epidemiology Group, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
Title of the talk: Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam
Abstract
Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a prevalent cause of severe invasive infections in Vietnam, with notable morbidity and mortality rates. Despite its significance, there is limited data on the epidemiology, population structure, and dynamics of hvKp in this context. We conducted a screening for hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary tropical diseases hospital in Vietnam, as well as two cohorts of healthy individuals. Whole genome sequencing and comprehensive plasmid analysis were performed to characterise the genetic profile and phylogenetic structure of hvKp isolates, and elucidate the structure and horizontal transfer mechanism of the virulence plasmid. Among 700 BSI-causing Kp strains, 100 (14.3%) were identified as hvKp. Thirteen hvKp isolates were identified from 350 rectal swabs of healthy adults, while no hvKp was detected from 500 rectal swabs of healthy children. The population structure of hvKp isolates was genetically diverse, encompassing at least 17 different sequence types (STs), with ST23, ST86, and ST65 being predominant. Among the 113 hvKp isolates, 14 (12.6%) carried at least one antimicrobial resistance (AMR) gene, largely mediated through the acquisition of IncFII, IncR, and IncA/C plasmids. A common IncFIBK virulence plasmid was found across different STs, experimentally demonstrated to be transferable between Kp strains via the acquisition of AMR conjugative helper plasmids. These helper plasmids, primarily belonging to the IncFII group, shared a common oriT region with the virulence plasmid. Overall, hvKp isolates from BSIs and human carriage clustered within the same phylogenetic clusters, suggesting a significant role of human intestinal carriage in hvKp transmission. In conclusions, various hvKp genotypes are notably co-circulating and inducing BSIs in Vietnam, with the capacity to acquire AMR and transfer virulence markers. Enhanced surveillance is crucial to understand the epidemiological and biological factors driving intestinal carriage and the transmission dynamics of hvKp. Such efforts are essential to identify appropriate preventive and control measures. Furthermore, we advocate the use of our molecular assay for diagnosing hvKp infections in clinical settings to guide thorough examinations and effective management.
Biography
Dr Duy Pham is Head of Molecular Epidemiology Group at Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam. He leads a multidisciplinary research program which integrates molecular biology, genomics and phylogenetics with epidemiological and clinical research to tackle drug-resistant bacterial infections in Vietnam, and across Asia. Specific bacterial infections and organisms of focus include typhoid fever (S. Typhi and S. Paratyphi A), sepsis (i.e. E. coli, K. pneumoniae, Enterobacter), diarrheal diseases (i.e. diarrhea-causing E. coli, Shigella spp, nontyphoidal Salmonella spp), and nosocomial infections (i.e. A. baumanii, K. pneumoniae). His research has had major contribution to better understand how drug-resistant bacteria evolve and spread in different populations and how they impact patient outcomes. Dr Pham has developed a strong collaboration with local partners and international research institutes such as Wellcome Trust Sanger Institute, University of Cambridge, International Vaccine Institute, Oxford University and its affiliated Units in South and Southeast Asia.
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