Contributions of horizontal gene transfer (HGT) to microbial evolution

 

Many bacterial species have the remarkable ability to rapidly acquire novel traits through incorporation of DNA fragments from other strains or species into their genome. HGT facilitates the single-step acquisition of complex metabolic pathways and functions that would otherwise have taken millions of years through mutation alone. Bacteria use a variety of mobile genetic elements and recombination systems to acquire exogenous DNA.

 

We study genetic transfers between strains of the same species, between species, and even between mobile genetic elements. We aim to define the ecological drivers, barriers, genetic mechanisms and impacts of HGT, especially in bacterial pathogens.

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Genomic epidemiology of antimicrobial resistant bacteria

 

Antimicrobial resistance is one of the top ten global public health threats to humanity in the 21st century. We aim to make impactful solutions to the antimicrobial resistance crisis and reduce its burden on public health and society. There is no easy solution, but a genomics-informed, long-term, real-time, global pathogen surveillance system is instrumental in understanding and mitigating this threat. Genomic epidemiology and health bioinformatics offer a powerful approach to pathogen surveillance and public health decision-making – taking whole genome sequencing data of a pathogen to understand the distribution of a disease in a specified population, how the pathogen evolves, and which public health interventions and strategies may contain it.

 

Using network and phylogenetic analysis, my group has discovered cryptic outbreaks and undetected chains of transmission in Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Salmonella enterica, and Klebsiella species. We identified importation events and local circulation of multidrug resistant clones. Using molecular dating, we track demographical changes in pathogen serotypes, genotypes, and lineages. We work on different bacterial genomics projects on bloodstream pathogens (in collaboration with Dartmouth-Hitchcock Medical Center, New Hampshire) and on foodborne pathogens (in collaboration with the New York State Department of Health). We also study the global populations of these pathogens - how they are distributed, transmitted and evolve.

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Human-animal disease transmission and host adaptation

 

The capacity for some pathogens to infect different host-species is a major threat to public health, animal health, and food security. Majority of emerging human infectious diseases have been traced to an animal origin, but without the ability to accurately predict which of the thousands of animal pathogens may cause human infections, preemptive human pandemic preparedness efforts are difficult. A prediction framework is required to identify pathogens with the capacity to undergo cross-species transmission and elucidate the genetic basis that facilitates their adaptation to new hosts.

 

Our studies on Staphylococcus aureus from human and various animal hosts revealed the importance of prophage-encoded human evasion genes in host adaptation, host switching, and transmission. We collaborate with Dr. Daise Rossi (Federal University of Uberlândia, Brazil) on the evolution, multi-host adaptation, and population dynamics of Campylobacter species in Brazil. Outcomes from our research have broad and tangible impacts on predicting and managing emerging zoonoses at the animal-human interface.

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Pan-genomes and the nature of microbial species and speciation

 

Species and speciation have been notoriously challenging to study in microbes. The discovery of large pan-genomes in microbes has stimulated many discussions about the nature of microbial species, where to draw boundaries between species, and whether microbial species have any biological relevance.

 

Genomic differences between strains are often not trivial because such fine-scale variation may define major functional and adaptive potential that differentiate closely related strains. We investigate the contributions of different evolutionary processes and mechanisms that drive species formation and persistence in different species of prokaryotes. We have shown that a single bacterial strain carries genes with distinct ecologies and modes of evolution, and that the species pan-genome diversifies through distinct mechanisms, in different ecologies and at different timescales.

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