Genomic epidemiology of MRSA infection and colonization isolates among military trainees with skin and soft tissue infection

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Chen AE, Cantey JB, Carroll KC, Ross T, Speser S, Siberry GK. Discordance between Staphylococcus aureus nasal colonization and skin infections in children. Pediatr Infect Dis J. 2009;28:244–6. https://doi.org/10.1097/INF.0b013e31818cb0c4.

    Article  PubMed  Google Scholar 

  2. 2.

    Fritz SA, Epplin EK, Garbutt J, Storch GA. Skin infection in children colonized with community-associated methicillin-resistant Staphylococcus aureus. J Infect. 2009;59:394–401. https://doi.org/10.1016/j.jinf.2009.09.001.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Ellis MW, Hospenthal DR, Dooley DP, Gray PJ, Murray CK. Natural history of community-acquired methicillin-resistant Staphylococcus aureus colonization and infection in soldiers. Clin Infect Dis. 2004;39:971–9. https://doi.org/10.1086/423965.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004;364:703–5. https://doi.org/10.1016/s0140-6736(04)16897-9.

    Article  PubMed  Google Scholar 

  7. 7.

    von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001;344:11–6. https://doi.org/10.1056/nejm200101043440102.

    Article  Google Scholar 

  8. 8.

    Mermel LA, Cartony JM, Covington P, Maxey G, Morse D. Methicillin-resistant Staphylococcus aureus colonization at different body sites: a prospective, quantitative analysis. J Clin Microbiol. 2011;49:1119–21. https://doi.org/10.1128/jcm.02601-10.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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.

    CAS  Article  PubMed  Google Scholar 

  10. 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. 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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Millar EV, Rice GK, Elassal EM, Schlett CD, Bennett JW, Redden CL, et al. Genomic characterization of USA300 MRSA to evaluate intraclass transmission and recurrence of SSTI among high risk military trainees. Clin Infect Dis. 2017. https://doi.org/10.1093/cid/cix327.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Biodefense and Emerging Infections Research Resources Repository, Manassas, VA. beiresources.org.

  14. 14.

    FastQC. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/. Accessed 2 Nov 2017.

  15. 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.

  16. 16.

    Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19:455–77. https://doi.org/10.1089/cmb.2012.0021.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215:403–10. https://doi.org/10.1016/s0022-2836(05)80360-2.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    BAGA. https://github.com/daveuu/baga. Accessed 2 Nov 2017.

  19. 19.

    Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60. https://doi.org/10.1093/bioinformatics/btp324.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303. https://doi.org/10.1101/gr.107524.110.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol. 2010;59:307–21. https://doi.org/10.1093/sysbio/syq010.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. 24.

    Kumar N, David MZ, Boyle-Vavra S, Sieth J, Daum RS. High Staphylococcus aureus colonization prevalence among patients with skin and soft tissue infections and controls in an urban emergency department. J Clin Microbiol. 2015;53:810–5. https://doi.org/10.1128/jcm.03221-14.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Faden H, Lesse AJ, Trask J, Hill JA, Hess DJ, Dryja D, et al. Importance of colonization site in the current epidemic of Staphylococcal skin abscesses. Pediatrics. 2010;125:e618-24. https://doi.org/10.1542/peds.2009-1523.

    Article  PubMed  Google Scholar 

  26. 26.

    Popovich KJ, Snitkin E, Green SJ, Aroutcheva A, Hayden MK, Hota B, et al. Genomic epidemiology of USA300 methicillin-resistant Staphylococcus aureus in an urban community. Clin Infect Dis. 2016;62:37–44. https://doi.org/10.1093/cid/civ794.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Golubchik T, Batty EM, Miller RR, Farr H, Young BC, Larner-Svensson H, et al. Within-host evolution of Staphylococcus aureus during asymptomatic carriage. PloS One. 2013;8:e61319. https://doi.org/10.1371/journal.pone.0061319.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Lemmens N, van Wamel W, Snijders S, Lesse AJ, Faden H, van Belkum A. Genomic comparisons of USA300 Staphylococcus aureus colonizating the nose and rectum of children with skin abscesses. Microb Pathog. 2011;50:192–9. https://doi.org/10.1016/j.micpath.2010.12.006.

    CAS  Article  PubMed  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. 30.

    Stine OC, Burrowes S, David S, Johnson JK, Roghmann MC. Transmission clusters of methicillin-resistant Staphylococcus Aureus in long-term care facilities based on whole-genome sequencing. Infect Control Hosp Epidemiol. 2016;37:685–91. https://doi.org/10.1017/ice.2016.41.

    Article  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Mollema FP, Richardus JH, Behrendt M, Vaessen N, Lodder W, Hendriks W, et al. Transmission of methicillin-resistant Staphylococcus aureus to household contacts. J Clin Microbiol. 2010;48:202–7. https://doi.org/10.1128/jcm.01499-09.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to the study team of clinical research coordinators, laboratory personnel, and data management staff for their dedication to the project.

Funding

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Eugene V. Millar.

Ethics declarations

Conflict of interest

All authors: no conflicts.

Disclaimer

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 203 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Millar, E.V., Rice, G.K., Schlett, C.D. et al. Genomic epidemiology of MRSA infection and colonization isolates among military trainees with skin and soft tissue infection. Infection 47, 729–737 (2019). https://doi.org/10.1007/s15010-019-01282-w

Download citation

Keywords

  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Skin and soft tissue infection
  • Colonization
  • Whole genome sequencing
  • Genomics
  • Military