# Genomics of S. Aureus Colonization after Initial and Recurrent Skin Infections and the Impact of Antibiotics

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $717,379

## Abstract

Project Summary
Staphylococcus aureus is a bacterium that can live on the human body harmlessly (i.e., colonization), but it is
also among the most common causes of skin and soft tissue infections (SSTIs), bloodstream infections, and
pneumonia. Methicillin-resistant S. aureus (MRSA) strains that are resistant to nearly all antibiotics related to
penicillin are particularly concerning, killing more than 11,000 people each year in the U.S. Furthermore, up to
50% of patients with an initial MRSA SSTI suffer from a recurrent SSTI within 12 months. It would be useful to
know which patients are at high risk of recurrence so that they could be treated in the best way to prevent the
recurrent infection. However, now we do not know who is at high risk of recurrence. The USA300 MRSA strain
is the most common cause of MRSA infections in the U.S., especially SSTIs. New methods using whole
genome sequencing (WGS) are available to track the evolutionary change in MRSA over time as it grows on
the human body. Little is known about the communities of MRSA that develop over time, how diverse they are,
how they are affected when a person takes an antibiotic, and what genetic changes in MRSA are associated
with the onset of a recurrent infection or prolonged colonization. We propose a WGS study of 7,000 MRSA
isolates obtained from 400 people with a MRSA SSTI collected over a one-year period. We will test the 400
subjects in the proposed study at 3 body sites quarterly over a year to address these unknowns for the first
time, determining which bacterial genes change over time as USA300 and other MRSA strain types grow and
evolve on the body. Colonizing bacteria are constantly interacting with their human hosts and the environment.
We will therefore assess these gene changes in the colonizing bacteria over time as well as the demographic,
behavioral, antibiotic exposure, and medical characteristics of studied human subjects to determine their
relative impacts on the risk of a recurrent infection. Our central hypothesis is that USA300 and closely related
(CC8) strains, independent of host characteristics: 1) colonize the skin for a longer period of time and cause
recurrent infections; 2) more likely cause infections that require medical intervention; and 3) are more likely to
survive as colonizers after antibiotic treatment than other strain types. We also hypothesize that a higher level
of diversity among colonizing MRSA is a predictor of long-term colonization and ability to survive challenge
with antibiotics. Our hypotheses will be assessed using a combination of analysis of genome data and
computer modeling. We will also test the MRSA isolates that we collect to determine if specific genetic
changes lead to changes in the fitness of MRSA, as measured by changes in their growth rate, relative to
strains cultured earlier from the same subject. We aim to identify which clinical treatments lead to the most
dramatic reduction in fitness of the surviving S. aureus popul...

## Key facts

- **NIH application ID:** 10468070
- **Project number:** 5R01AI139188-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael Zdenek David
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $717,379
- **Award type:** 5
- **Project period:** 2018-08-16 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468070

## Citation

> US National Institutes of Health, RePORTER application 10468070, Genomics of S. Aureus Colonization after Initial and Recurrent Skin Infections and the Impact of Antibiotics (5R01AI139188-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10468070. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*