# Mobile Genetic Elements and Clinical Outcomes in Staphylococcus aureus Bacteremia

> **NIH NIH K01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $129,870

## Abstract

Project Summary
Antimicrobial resistance (AMR) and its impact on health has been recognized as one of the most serious public
health threats facing society. Significantly, the vast majority of acquired AMR genes are carried on mobile
genetic elements (MGEs), which include plasmids, insertion sequences, and transposons. One of the most
important hospital and community-associated pathogens harboring resistance genes is Staphylococcus
aureus, which causes more than 80,000 infections and 11,000 deaths each year in the United States. S.
aureus readily acquire MGEs, which encompass more than 20% of the genome for most strains, and these
elements have been central to the establishment and broad spread of resistance to antibiotics such as oxacillin
and vancomycin. Additionally, S. aureus is capable of causing a wide range of infections, including bacteremia,
with a mortality rate up to 30%. Utilizing an unparalleled collection of S. aureus strains from a cohort of patients
in Central and South America with bacteremia, I seek to develop a framework for the identification and
comparison of circulating MGEs through the use of bacterial phylogenetics, clinical epidemiology, and machine
learning. This dataset will serve as the foundation for my training to become an independent scientist. To begin
interrogating this exceptional strain collection, we have generated Illumina short-read whole genome
sequencing data on 1,087 S. aureus bacteremia isolates to identify MGEs, and will leverage novel ultra-long
read sequencing methodologies to fully characterize the position and variations of these elements. The three
aims within this proposal are designed to elucidate the role of MGEs in driving the genetic diversification of
endemic S. aureus clades, and identify if they serve as adaptation hotspots when put under selective pressure
from the host immune system or antibiotics. First, I will characterize the repertoire of MGEs within this large
cohort of isolates and apply gene-order and Bayesian time-measured phylogenetics to identify the predominant
MGEs within each clade and how frequently they are acquired and lost. Second, I will assess the MGE
diversity within isolates collected serially from the same individual. I hypothesize these MGEs will be the
primary variation points and will be more important than single nucleotide polymorphisms (SNPs) to the
adaptation to selective pressures such as antibiotics. Third, I will identify the clinical (age, BMI, and present
comorbidities) and genomic (SNPs, MGEs, and genes) features that are predictive of the 30-day mortality in
the predominant clades of S. aureus within our dataset. I theorize these genetic and clinical signatures will be
different for each clade as they possess different repertoires of MGEs. The Center for Antimicrobial Resistance
and Microbial Genomics in The University of Texas Health Sciences Center at Houston has a firm commitment
to understanding and reducing AMR and AMR infections. This provides an ...

## Key facts

- **NIH application ID:** 10211124
- **Project number:** 5K01AI148593-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Blake M Hanson
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $129,870
- **Award type:** 5
- **Project period:** 2020-07-06 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211124

## Citation

> US National Institutes of Health, RePORTER application 10211124, Mobile Genetic Elements and Clinical Outcomes in Staphylococcus aureus Bacteremia (5K01AI148593-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10211124. Licensed CC0.

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