Genomic sequencing of a diversity of Staphylococcus isolates to determine the genetic basis for drug resistance in S. aureus

Summary

The prevalence of methicillin resistant Staphylococcus aureus (MRSA) is of growing concern, particularly due to the more recent increased frequency of community acquired MRSA in the population. The prevalence of MRSA has placed additional urgency to understand the mechanisms of resistance to methicillin as well as second line antibiotics. To date, the sequencing of MRSA genomes has not yielded significant insights into the epidemiology of S. aureus MRSA infections.

The scope of work in this project takes a multi-pronged approach to enabling improved understanding of S. aureus drug resistance. First, we plan to sequence two methicillin sensitive (MSSA) isolates representing each of the 26 identified sequence types encompassing the full diversity of S. aureus species. This important framework will greatly enhance the power of comparative genomics for this important pathogen for the S. aureus research community. Second, we will sequence thirty seven isolates of the sibling species S. epidermidis, thought to be an important and prevalent reservoir of genes acquired by horizontal transmission in S. aureus. Third, we will sequence a diverse collection of thirty MRSA isolates collected in Army clinics over the past several years. These isolates will be directly compared to the appropriate reference genome sequence type to better understand the basis for the virulence properties associated with these MRSA. Last, we will sequence S. aureus genomes that have been subjected to antibiotic challenge in the laboratory to select for resistant organisms. The sequencing of these genomes will reveal specific point mutations that give rise to antibiotic resistant phenotypes and will provide clinical and academic laboratories with improved diagnostic markers for the screening of existing strain collections and patient samples.

White Paper Access

The initial white paper submitted can be downloaded here. Since white papers are not always approved exactly as submitted, this document may not exactly describe the final form of the project. Please contact gsc@jcvi.org if you have any questions.

All Publications that use data generated and/or are supported by the Sequencing Center at JCVI should acknowledge the sponsor as: This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract numbers N01-AI30071
and/or HHSN272200900007C.


Investigators and Collaborators

Marcus Jones, PhD

Assistant Professor, J.Craig Venter Institute

Gordon Archer, PhD

Virginia Commonwealth University

Xiao-zhe Huang, PhD

Walter Reed Army Institute of Research

Barry Kreiswirth, PhD

University of Medicine and Dentistry, New Jersey

Patrick McGann, PhD

Walter Reed Army Institute of Research

Mikeljon Nikolich, PhD

Walter Reed Army Institute of Research