Brief Communication | Published:

Co-infecting microorganisms dramatically alter pathogen gene essentiality during polymicrobial infection

Nature Microbiology volume 2, Article number: 17079 (2017) | Download Citation

Abstract

Identifying genes required by pathogens during infection is critical for antimicrobial development. Here, we use a Monte Carlo simulation-based method to analyse high-throughput transposon sequencing data to determine the role of infection site and co-infecting microorganisms on the in vivo ‘essential’ genome of Staphylococcus aureus. We discovered that co-infection of murine surgical wounds with Pseudomonas aeruginosa results in conversion of 25% of the in vivo S. aureus mono-culture essential genes to non-essential. Furthermore, 182 S. aureus genes are uniquely essential during co-infection. These ‘community dependent essential’ (CoDE) genes illustrate the importance of studying pathogen gene essentiality in polymicrobial communities.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Nat. Rev. Drug Discov. 12, 371–387 (2013).

  2. 2.

    et al. Sci. Rep. 5, 9838 (2015).

  3. 3.

    , , , & Proc. Natl Acad. Sci. USA 112, 4110–4115 (2015).

  4. 4.

    et al. mBio 3, e00113-12 (2012).

  5. 5.

    & Nat. Rev. Microbiol. 11, 435–442 (2013).

  6. 6.

    et al. PLoS Genet. 10, e1004518 (2014).

  7. 7.

    et al. mBio 5, e01729-14 (2014).

  8. 8.

    et al. PLoS Pathog. 11, e1005341 (2015).

  9. 9.

    , , , & Nat. Rev. Microbiol. 14, 93–105 (2015).

  10. 10.

    & Nat. Rev. Microbiol. 7, 629–641 (2009).

  11. 11.

    N. Engl. J. Med. 339, 520–532 (1998).

  12. 12.

    , , & Trends Microbiol. 19, 225–232 (2011).

  13. 13.

    et al. Int. Wound J. 3, 225–231 (2006).

  14. 14.

    , , & APMIS 104, 895–899 (1996).

  15. 15.

    , , , & Proc. Natl Acad. Sci. USA 113, 13887–13892 (2016).

  16. 16.

    , , , & PLoS ONE 7, e43012 (2012).

  17. 17.

    et al. PLoS ONE 6, e27317 (2011).

  18. 18.

    , , & Proc. Natl Acad. Sci. USA 110, 1059–1064 (2013).

  19. 19.

    et al. J. Clin. Microbiol. 47, 4084–4089 (2009).

  20. 20.

    Wound Repair Regen. 12, 129–133 (2004).

  21. 21.

    , , & J. Bacteriol. 193, 1583–1589 (2011).

  22. 22.

    , , , & Nat. Microbiol. 2, 16183 (2016).

  23. 23.

    , , , & Wound Repair Regen. 16, 805–813 (2008).

  24. 24.

    et al. Infect. Immun. 82, 4718–4728 (2014).

  25. 25.

    , , , & Proc. Natl Acad. Sci. USA 113, E791–E800 (2016).

  26. 26.

    , , & PLoS Pathog. 7, e1002012 (2011).

  27. 27.

    , , , & mBio 7, e00782-16 (2016).

  28. 28.

    , & mBio 2, e00315-10 (2011).

  29. 29.

    in The Genetic Manipulation of Staphylococci 69–74 (Springer, 2015).

  30. 30.

    et al. PLoS Genet. 8, e1002804 (2012).

  31. 31.

    et al. Gene 107, 61–68 (1991).

  32. 32.

    et al. J. Bacteriol. 192, 6418–6427 (2010).

  33. 33.

    Microbiology 150, 2677–2688 (2004).

  34. 34.

    et al. Med. Microbiol. Immunol. 202, 131–141 (2013).

  35. 35.

    , , & mBio 6, e01603-15 (2015).

  36. 36.

    et al. BMC Genomics 13, 578 (2012).

  37. 37.

    EMBnet 17, 10–12 (2011).

  38. 38.

    , & Genome Biol. 15, 550 (2014).

  39. 39.

    & J. Am. Stat. Assoc. 97, 611–631 (2002).

  40. 40.

    VENNY. An interactive tool for comparing lists with Venn's diagrams (BioinfoGP, 2007–2015);

  41. 41.

    et al. Nat. Methods 9, 676–682 (2012).

Download references

Acknowledgements

This work was supported by the National Institutes of Health (NIH, grants R01GM116547-01A1 and 1R01DE023193-01 to M.W.) and a grant from Human Frontiers Science (to M.W.). C.B.I. is supported by postdoctoral fellowship IBBERS16F0 from the Cystic Fibrosis Foundation. Contributions by M.S.G. were supported by PHS grant AI107248 and the Harvard-wide Program on Antibiotic Resistance (AI083214). A.S. is supported by a predoctoral fellowship from the NIH (F31DE024931). The authors thank M. Ramsey for generating pMR361-K, K. Michie for assistance with the chronic surgical wound experiments, S. Leonard for computational assistance and D. Cornforth for discussion of the manuscript.

Author information

Affiliations

  1. Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, LaMontagne Center for Infectious Disease, The University of Texas at Austin, 1 University Station, A5000, Austin, Texas 78712, USA

    • Carolyn B. Ibberson
    • , Apollo Stacy
    • , Justine L. Dees
    •  & Marvin Whiteley
  2. Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA

    • Derek Fleming
    •  & Kendra Rumbaugh
  3. Department of Ophthalmology and Department of Microbiology and Immunobiology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02115, USA

    • Michael S. Gilmore

Authors

  1. Search for Carolyn B. Ibberson in:

  2. Search for Apollo Stacy in:

  3. Search for Derek Fleming in:

  4. Search for Justine L. Dees in:

  5. Search for Kendra Rumbaugh in:

  6. Search for Michael S. Gilmore in:

  7. Search for Marvin Whiteley in:

Contributions

C.B.I., A.S., K.R. and M.W. designed experiments. C.B.I., A.S. and M.W. analysed data. C.B.I., A.S. and D.F. performed experiments. J.L.D. prepared sequencing libraries. M.S.G. provided S. aureus HG003 transposon library and provided the raw data from previous studies7,8 included in the analysis. C.B.I., A.S., J.L.D., M.S.G., K.R. and M.W. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Marvin Whiteley.

Supplementary information

PDF files

  1. 1.

    Supplementary information

    Supplementary Figures 1–3, Supplementary Tables 2 and 3, Supplementary References

Excel files

  1. 1.

    Supplementary Table 1

    The essential genes for S. aureus and A. actinomycetemcomitans.

  2. 2.

    Supplementary Table 4

    Sequencing data for each replicate in this study.

  3. 3.

    Supplementary Table 5

    A list of all of the ‘TA’ dinucleotide positions in the S. aureus NCTC8325 reference genome.

  4. 4.

    Supplementary Table 6

    A list of all of the ‘TA’ dinucleotide positions in the A. actinomycetemcomitans strain 624 reference genome.

  5. 5.

    Supplementary Table 7

    Homologues in S. aureus strain NCTC8325 and S. aureus strain USA300_FPR3757 for the transposon mutants used in this study.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nmicrobiol.2017.79

Further reading