• University of California-Davis (2017)

  • Molecular Microbiology and Microbial Pathogenesis

  • Gautam Dantas, Ph.D.

  • Influence of Environmental Gradients on Genomic Variation in Pediatric Commensals and Pathogens

  • ssawhney@wustl.edu

Research

Aim 1: Explore sub-species genomic variation within the infant gut microbiome (GM) across preterm birth, early-life antibiotic exposure, hospitalization, and diet. I will test the hypothesis that the spread of antibiotic resistance gene (ARG)-carrying plasmid taxonomical units (PTUs) among Enterobacteri-aceae, Enterococci, and Staphylococci across preterm GMs is driven by spatiotemporal proximity (Aim 1.1), and that high-quality metagenomically-assembled genomes (MAGs) can be generated and leveraged to track strain dynamics and within-host evolution in response to dietary stimuli during early adolescence (Aim 1.2). I will assemble closed plasmids and high-quality MAGs by combining short- and long-read sequencing of stool supplemented with a minimal, highly optimized suite of selective and differential media that isolates the highly prevalent and abundant species of the preterm GM and enriches a spectrum of low-abundance microbial spe-cies within the developing infant GM. Using stool samples, plate scrapes, and cultured isolates I will (i) compre-hensively characterize the preterm GM plasmidome; (ii) capture PTUs that persist in hospital environments and across preterm GMs over time; and (iii) identify strain dynamics and in vivo evolution underlying community re-sponses to infant diet.
Aim 2: Identify genomic signatures that reflect non-mecA/mecC-mediated oxacillin resistance among colonizing S. aureus isolates in the NICU and colonizing and diagnostic S. pseudintermedius isolates across host- and environment-types. I will test the hypothesis that there is a discernable genomic signature correlated with non-traditional S. aureus borderline oxacillin resistance (BORSA) (Aim 2.1) and that genomic diversity across S. pseudintermedius genomes reflects ecological niche adaptation (Aim 2.2). I will sequence 101 S. aureus isolates collected from the anterior nares of infants in the NICU and 500 S. pseudintermedius isolates collected from human and animal skin and wound sites in medical clinics and in the community. Using these genomic data, I will interrogate the core and accessory genomes of these Staphylo-cocci through bioinformatic tools and machine learning models to (i) identify genetic features that can be used to predict borderline oxacillin resistance among S. aureus in the NICU, (ii) assess for persistence of S. aureus strains in the NICU environment, and (iii) profile niche adaptation among S. pseudintermedius.

Graduate Publications:

Sawhney SS, Ransom EM, Wallace MA, Reich PJ, Dantas G, Burnham CD.. 2022 Comparative Genomics of Borderline Oxacillin-Resistant Staphylococcus aureus Detected during a Pseudo-outbreak of Methicillin-Resistant S. aureus in a Neonatal Intensive Care Unit. mBio, 13(1):e0319621.

Sawhney SS, Johnson C, Shupe A, Fine J, Dantas G, Burnham CD, Yarbrough ML.. 2022 Assessment of the Urinary Microbiota of MSM Using Urine Culturomics Reveals a Diverse Microbial Environment. Clin Chem, 68(1):192-203.

Last Updated: 2/16/2022 12:23:35 PM

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