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Research Overview

For more information about our research, check out Cheryl's 2019 Perspective article in mSystems:

Clonal yet Different: Understanding the Causes of Genomic Heterogeneity in Microbial Species and Impacts on Public Health

mSystems 7;4(3):e00097-19

doi: 10.1128/mSystems.00097-19

We are conceptually-driven rather than taxonomically-driven. Hence, we study a range of bacterial species from human and animal hosts. If you are interested in any of these research projects, feel free to contact us.

 

We ask the questions:

  • What makes strains of the same species different?

  • To what extent are these differences clinically relevant?

• Disease outbreaks

• Disease transmission

• Spread of antimicrobial resistance

We use concepts, principles and methods in population genomics, pan-GWAS, networks, and phylogenetics to answer these questions.

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Staphylococcus on blood agar plate

Photo credit: Stephanie S. R. Souza

Horizontal gene transfer and recombination

We study the causes, mechanisms and consequences of gene sharing within and between species.

 

Genetic recombination allows a bacterial cell to rapidly acquire novel traits through incorporation of DNA fragments from other strains or species into its own genome. It can result to either (1) allelic replacements that preserve the size and functionality of the recombined sequence (i.e., similar to “gene conversion” in sexually reproducing organisms) or (2) the addition of new DNA segments when two flanking regions of high DNA similarity initiate the recombination process and mediate successful horizontal gene transfer.

 

The consequences of recombination are vast. It is known to influence a myriad of evolutionary and population processes, including levels of standing diversity, niche expansion, spread of resistance and virulence determinants, and rapid adaptive changes in response to new or fluctuating environmental conditions. It can generate vaccine escape variants and the rapid diversification of surface antigens, allowing immune evasion. Recombination of large DNA segments can also result to the emergence of novel genetic variants or hybrids with unique phenotypes such as multidrug resistance, hyper-virulence and increased transmissibility.

Genetic basis of host adaptation and host switching

The capacity for some pathogens to infect different host-species is a major threat to public health and food security. In collaboration with the New Hampshire Veterinary Diagnostic Lab, we have collected >1,100 clinical isolates of >25 species of Staphylococcus from >15 wild and domestic animals. Little is known of the evolutionary history of these rare species of Staphylococcus, which are now being recognized as major opportunistic pathogens of humans and animals. These species can also act as a major reservoir for many transferrable antimicrobial resistance determinants and virulence-related genes.

We also collaborate with Dr. Diana Northup (Univ. of New Mexico) to study Streptomyces bacteria from 12 species of bats. Streptomyces are prolific producers of bioactive specialized metabolites and are known as the major source of naturally-derived antibiotics and many pharmaceutically relevant compounds (e.g., antifungals, antitumor, antihelminths, antiprotozoans, immunosuppressants) that we use today.

For both genera, we study how  the presence/absence and distribution of core alleles, accessory genes and mobile genetic elements contribute to their ability to colonize different animal host-species.

Drivers of the evolution and spread of antimicrobial resistance 

We study the genomic, population, epidemiological and evolutionary drivers of drug-resistant bacterial pathogens. We use whole genome sequencing to elucidate disease outbreaks, transmission, virulence and the local and global spread of antimicrobial resistance. We are interested in resistance genes that are horizontally acquired and how they are transmitted across the population and in different ecological niches.

 

Bloodstream infections cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of antimicrobial resistant pathogens in bloodstream infections, which are associated with therapeutic failure and increased mortality. We study multiple bacterial species that are implicated in bloodstream infections, such as Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Enterobacter cloacae in collaboration with Dr. Isabella Martin (Dartmouth-Hitchcock Medical Center). 

We also collaborate with the New Hampshire Dept. of Health and Human Services and the New York Wadsworth Center to carry out genomic analyses of diverse bacterial pathogens that cause foodborne infections (Campylobacter, Salmonella, Listeria).

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