Genomic epidemiology of MRSA infection and colonization isolates among military trainees with skin and soft tissue infection
Individuals with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) can be simultaneously colonized with MRSA on multiple body sites. Using whole genome sequencing (WGS), the intrahost relatedness of MRSA colonization and infection isolates was investigated.
In the context of a prospective case–control study of SSTI, we analyzed colonization and infection isolates from US Army Infantry trainees with purulent infection due to MRSA. At the time of clinical presentation for SSTI, culture swabs were obtained from the infection site, as well as from the patient’s nasal, oral, inguinal, and perianal regions. S. aureus culture and susceptibility was performed by standard methods. DNA from MRSA isolates was extracted and libraries were produced. Sequences were generated on an Illumina MiSeq, sequence reads were assembled, and single nucleotide variant (SNV) data were analyzed.
Of 74 trainees with MRSA SSTI, 19 (25.7%) were colonized with MRSA. Ten (52.6%) were colonized on more than one body site. Colonization frequency by anatomic site was as follows: inguinal region (33%), nasal region (30%), perianal region (22%), and oral region (14%). A total of 36 MRSA colonization isolates were characterized. The intrahost median number of SNVs between infection and colonization isolates was 17. Among trainees with recurrent MRSA SSTI, limited intrahost diversity suggests that persistent colonization is a major contributor to recurrence risk.
Among military trainees with MRSA SSTI, genomic characterization of infection and colonization isolates revealed a high degree of strain relatedness. Single acquisition events may account for MRSA colonization and infection in this population.
KeywordsMethicillin-resistant Staphylococcus aureus (MRSA) Skin and soft tissue infection Colonization Whole genome sequencing Genomics Military
We are indebted to the study team of clinical research coordinators, laboratory personnel, and data management staff for their dedication to the project.
This work was supported by a US Department of Defense Program Project Grant [HT9404-12-1-0019 to M.W.E.]. Additional support for this work was provided by the Department of Defense Global Emerging Infections Surveillance and Response System [GEIS;HU0001-10-1-0018 to M.W.E] and the Military Infectious Diseases Research Program [MIDRP; HT9404-12-1-0012 to M.W.E]. The protocol was conducted by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services UNIVERSITY of the Health Sciences through a cooperative agreement with The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072.
Compliance with ethical standards
Conflict of interest
All authors: no conflicts.
The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), the Department of Defense (DoD), the Departments of the Army, Navy, or Air Force, or the Henry M. Jackson Foundation for the Advancement of Military Medicine. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government. Drs. Bennett, Bishop-Lilly, Hamilton, and Tribble are service members or employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties.
- 3.Miller LG, Eells SJ, Taylor AR, David MZ, Ortiz N, Zychowski D, et al. Staphylococcus aureus colonization among household contacts of patients with skin infections: risk factors, strain discordance, and complex ecology. Clin Infect Dis. 2012;54:1523–35. https://doi.org/10.1093/cid/cis213.CrossRefGoogle Scholar
- 5.Ellis MW, Schlett CD, Millar EV, Crawford KB, Cui T, Lanier JB, et al. Prevalence of nasal colonization and strain concordance in patients with community-associated Staphylococcus aureus skin and soft-tissue infections. Infect Control Hosp Epidemiol. 2014;35:1251–6. https://doi.org/10.1086/678060.CrossRefGoogle Scholar
- 9.Yang ES, Tan J, Eells S, Rieg G, Tagudar G, Miller LG. Body site colonization in patients with community-associated methicillin-resistant Staphylococcus aureus and other types of S. aureus skin infections. Clin Microbiol Infect. 2010;16:425–31. https://doi.org/10.1111/j.1469-0691.2009.02836.x.CrossRefGoogle Scholar
- 10.Singh J, Johnson RC, Schlett CD, Elassal EM, Crawford KB, Mor D, et al. Multi-body-site microbiome and culture profiling of military trainees suffering from skin and soft tissue infections at fort benning, Georgia. mSphere. 2016;1. https://doi.org/10.1128/mSphere.00232-16.
- 11.Azarian T, Daum RS, Petty LA, Steinbeck JL, Yin Z, Nolan D, et al. Intrahost evolution of methicillin-resistant Staphylococcus aureus USA300 among individuals with reoccurring skin and soft-tissue infections. J Infect Dis. 2016;214:895–905. https://doi.org/10.1093/infdis/jiw242.CrossRefGoogle Scholar
- 13.Biodefense and Emerging Infections Research Resources Repository, Manassas, VA. beiresources.org.Google Scholar
- 14.FastQC. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/. Accessed 2 Nov 2017.
- 15.Joshi NA. Sickle. A sliding-window, adaptive, quality-based trimming tool for FastQ files (Version 1.33). Available at https://github.com/najoshi/sickle. 2011. Accessed 2 Nov 2017.
- 18.BAGA. https://github.com/daveuu/baga. Accessed 2 Nov 2017.
- 22.Albrecht VS, Limbago BM, Moran GJ, Krishnadasan A, Gorwitz RJ, McDougal LK, et al. Staphylococcus aureus colonization and strain type at various body sites among patients with a closed abscess and uninfected controls at US emergency departments. J Clin Microbiol. 2015;53:3478–84. https://doi.org/10.1128/jcm.01371-15.CrossRefGoogle Scholar
- 23.Frazee BW, Lynn J, Charlebois ED, Lambert L, Lowery D, Perdreau-Remington F. High prevalence of methicillin-resistant Staphylococcus aureus in emergency department skin and soft tissue infections. Ann Emerg Med. 2005;45:311–20. https://doi.org/10.1016/j.annemergmed.2004.10.011.CrossRefGoogle Scholar
- 29.Price JR, Golubchik T, Cole K, Wilson DJ, Crook DW, Thwaites GE, et al. Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit. Clin Infect Dis. 2014;58:609–18. https://doi.org/10.1093/cid/cit807.CrossRefGoogle Scholar
- 31.Campbell KM, Vaughn AF, Russell KL, Smith B, Jimenez DL, Barrozo CP, et al. Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. J Clin Microbiol. 2004;42:4050–3. https://doi.org/10.1128/jcm.42.9.4050-4053.2004.CrossRefGoogle Scholar