Dissemination and Evolution of Enteric Pathogens on Local and Global Scales
Our focus is on enteric diseases, with current research streams on Vibrio cholerae and Klebsiella pneumoniae. These pathogens are of particular interest because of the mysterious nature of their niche in the environment, their global dissemination and their particularly flexible genomes and rapid evolution.
Vibrio cholerae is the causative agent of cholera, an ancient and often-fatal diarrheal disease with a complex ecology, which still affects 1.4 to 4.3 million people a year, causing between 28,000 to 142,000 deaths. Its causative agent is Vibrio cholerae, a bacterium with aquatic environmental reservoirs. New variants emerge constantly and have so far spread worldwide in three separate waves. We now know that cholera is constantly evolving in its endemic home, the Bay of Bengal, which is the ultimate source of all waves of the current pandemic. We believe that understanding the ecological and evolutionary dynamics of cholera in its natural home will not only save lives locally, but also prevent its spread abroad.
Klebsiella pneumonia (KP) is an opportunistic pathogen that can cause serious infections in humans, most notably in liver abscesses. It is part of the so-called ESKAPE pathogens, bacteria that harbor unusually high levels of multidrug resistance (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterococcus faecium/faecalis). They are some of the most drug resistant bacterial pathogens, making infections hard to treat. In the last decade or so, new variants of this species that are both multidrug resistant and hypervirulent have emerged around the world. In Singapore, this combination of trait has arisen independently in a few different lineages. This proposal aims at understanding how and where these strains have evolved. Our objective is also to create a rapid digital typing system for genome sequences of KP, which can easily be used by infectious disease diagnostic units in hospitals. Furthermore, we want to link this typing system to a molecular marker that can be used to study the ecology of hypervirulent lineages of KP, so they can readily be monitored in the general population through investigation of sewage, wastewater, waterways and food sources. Furthermore, to better understand why we have yet to determine the source of these pathogens, we will characterize several phenotypes relevant to their detection in the environment, namely their ability to form biofilms and capsules, to compete with other strains, to become non-culturable and to enter a mutator state. Combining a range of approaches from genomic epidemiology, microbial molecular ecology and traditional microbiology will allow us to better understand the evolution and ecology of hypervirulent and multidrug resistant KP and hopefully reduce the number of infections occurring in Singapore.
Our main goals
Establish genomic epidemiology as a front-line approach
Make molecular screening easy and cheap
Understand asymptomatic carriage and its role in dissemination
Determine inter-epidemic ecology in environmental reservoirs
Vibrio metoecus, the closest known relative of Vibrio cholerae (transmission electron micrograph in false colour by Paul Kirchberger)
Current projects
Antibiotic resistance in South East Asia: we are looking at how people’s environment and habits affects the “resistome” found in their gut microbiome. We monitor antibitotic resistance genes in both humans and their environment in countries such as Singapore, Bangladesh and Cambodia to look at wether how access to clean water, recreational usage of water, food sources and access to antibiotics affect the resistome they carry.
Asymptomatic carriage of pathogens: Although microbiomes of people suffering from bacterial infections have been well studied, little is known on how frequently pathogens are found in the gut of apparently healthy people and wether this is an important reservoir for pathogens. We are comparing the gut microbiomes of healthy individuals to the microbes found in their immediate environment to look at the movement of microbes between hosts and their habitat.
Emerging pathogen: We are following the emergence of a novel pathogens in Asia, including multidrug-resistant hypervirulent Klebsiella pneumoniae and novel species related to Vibrio cholerae.
Antagonism as a natural population structuring tool: Using the Type VI Secretion System (T6SS) as a model, we explore how antagonistic interactions shape natural populations of Vibrio cholerae and how pathogenic strains may persist in environmental reservoirs. We are also looking at how T6SS affects Klebsiella pneumoniae’s ability to compete with other microbes in the human gut or the environment.