Redefining the chronic-wound microbiome: Fungal communities are prevalent, dynamic, and associated with delayed healing

mBio

Volumn 7, Issue 5, 2016, Pages

  Kalan, Lindsay ^a   Loesche, Michael ^a   Hodkinson, Brendan P ^a   Heilmann, Kristopher ^b   Ruthel, Gordon ^d   Gardner, Sue E ^c   Grice, Elizabeth A ^a,e  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c UNIVERSITY OF IOWA COLLEGE OF NURSING   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERNAL TRANSCRIBED SPACER 1; FUNGAL DNA; RIBOSOMAL SPACER DNA;

ADULT; AGED; ANTIBIOTIC THERAPY; ARTICLE; ASCOMYCETES; BACTERIUM; BIOFILM; CHRONIC WOUND; COHORT ANALYSIS; CONTROLLED STUDY; DIABETIC FOOT; DISEASE ASSOCIATION; FEMALE; FILAMENTOUS FUNGUS; FUNGAL COMMUNITY; FUNGUS CULTURE; FUNGUS IDENTIFICATION; GENE LOCUS; HIGH THROUGHPUT SEQUENCING; HUMAN; INFLAMMATION; MAJOR CLINICAL STUDY; MALE; MICROBIOME; NONHUMAN; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROSPECTIVE STUDY; SPECIES DIVERSITY; TISSUE NECROSIS; WOUND HEALING IMPAIRMENT; YEAST; CHEMISTRY; CHRONIC DISEASE; CLASSIFICATION; COMPLICATION; DNA SEQUENCE; FUNGUS; GENETICS; LONGITUDINAL STUDY; MICROBIOLOGY; MYCOBIOME; WOUND HEALING; WOUND INFECTION;

CHRONIC DISEASE; DIABETIC FOOT; DNA, FUNGAL; DNA, RIBOSOMAL SPACER; FEMALE; FUNGI; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; LONGITUDINAL STUDIES; MALE; MYCOBIOME; SEQUENCE ANALYSIS, DNA; WOUND HEALING; WOUND INFECTION;

EID: 84994408766     PISSN: 21612129     EISSN: 21507511     Source Type: Journal    
DOI: 10.1128/mBio.01058-16     Document Type: Article

References (64)

1. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. 2009. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen 17:763–771. http://dx.doi.org/10.1111/j.1524-475X.2009.00543.x.
2. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. 2014. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149. http://dx.doi.org/10.1016/j.diabres.2013.11.002.
3. Kerr M, Rayman G, Jeffcoate WJ. 2014. Cost of diabetic foot disease to the National Health Service in England. DiabetMed31:1498–1504. http://dx.doi.org/10.1111/dme.12545.
4. Hicks CW, Selvarajah S, Mathioudakis N, Perler BA, Freischlag JA, Black JH, Abularrage CJ. 2014. Trends and determinants of costs associated with the inpatient care of diabetic foot ulcers. J Vasc Surg 60: 1247–1254.e2. http://dx.doi.org/10.1016/j.jvs.2014.05.009.
5. Scott RD, II. 2009. The direct medical costs of health care-associated infections in U.S. hospitals and the benefits of prevention. Division of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA.
6. Armstrong DG, Wrobel J, Robbins JM. 2007. Are diabetes-related wounds and amputations worse than cancer? Int Wound J 4:286–287. http://dx.doi.org/10.1111/j.1742-481X.2007.00392.x.
7. Robbins JM, Strauss G, Aron D, Long J, Kuba J, Kaplan Y. 2008. Mortality rates and diabetic foot ulcers. J Am Podiatr Med Assoc 98: 489–493.
8. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. 2005. The global burden of diabetic foot disease. Lancet 366:1719–1724. http://dx.doi.org/10.1016/S0140-6736(05)67698-2.
9. Dalton T, Dowd SE, Wolcott RD, Sun Y, Watters C, Griswold JA, Rumbaugh KP. 2011. An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. PLoS One 6:e27317. http://dx.doi.org/10.1371/journal.pone.0027317.
10. Percival SL, McCarty SM, Lipsky B. 2015. Biofilms and wounds: an overview of the evidence. Adv Wound Care (New Rochelle) 4:373–381.
11. Rhoads DD, Wolcott RD, Sun Y, Dowd SE. 2012. Comparison of culture and molecular identification of bacteria in chronic wounds. Int J Mol Sci 13:2535–2550. http://dx.doi.org/10.3390/ijms13032535.
12. Grice EA, Kong HH, Renaud G, Young AC, NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA. 2008. A diversity profile of the human skin microbiota. Genome Res 18:1043–1050. http://dx.doi.org/10.1101/gr.075549.107.
13. Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC, NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Murray PR, Green ED, Turner ML, Segre JA. 2009. Topographical and temporal diversity of the human skin microbiome. Science 324: 1190–1192. http://dx.doi.org/10.1126/science.1171700.
14. Meisel JS, Hannigan GD, Tyldsley AS, SanMiguel AJ, Hodkinson BP, Zheng Q, Grice EA. 2016. Skin microbiome surveys are strongly influenced by experimental design. J Invest Dermatol 136:947–956. http://dx.doi.org/10.1016/j.jid.2016.01.016.
15. SanMiguel A, Grice EA. 2015. Interactions between host factors and the skin microbiome. Cell Mol Life Sci 72:1499–1515. http://dx.doi.org/10.1007/s00018-014-1812-z.
16. Mathieu A, Delmont TO, Vogel TM, Robe P, Nalin R, Simonet P. 2013. Life on human surfaces: skin metagenomics. PLoS One 8:e65288. http://dx.doi.org/10.1371/journal.pone.0065288.
17. Hannigan GD, Grice EA. 2013. Microbial ecology of the skin in the era of metagenomics and molecular microbiology. Cold Spring Harb Perspect Med 3:a015362. http://dx.doi.org/10.1101/cshperspect.a015362.
18. Wiedenbeck J, Cohan FM. 2011. Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. FEMS Microbiol Rev 35:957–976. http://dx.doi.org/10.1111/j.1574-6976.2011.00292.x.
19. Brock M. 2009. Fungal metabolism in host niches. Curr Opin Microbiol 12:371–376. http://dx.doi.org/10.1016/j.mib.2009.05.004.
20. Sokurenko EV, Hasty DL, Dykhuizen DE. 1999. Pathoadaptive mutations: gene loss and variation in bacterial pathogens. Trends Microbiol 7:191–195. http://dx.doi.org/10.1016/S0966-842X(99)01493-6.
21. Gardner SE, Hillis SL, Heilmann K, Segre JA, Grice EA. 2013. The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes 62:923–930. http://dx.doi.org/10.2337/db12-0771.
22. Grice EA, Snitkin ES, Yockey LJ, Bermudez DM, NISC Comparative Sequencing Program, Liechty KW, Segre JA. 2010. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response. Proc Natl Acad Sci U S A 107:14799–14804. http://dx.doi.org/10.1073/pnas.1004204107.
23. Miller CN, Carville K, Newall N, Kapp S, Lewin G, Karimi L, Santamaria N. 2011. Assessing bacterial burden in wounds: comparing clinical observation and wound swabs. Int Wound J 8:45–55. http://dx.doi.org/10.1111/j.1742-481X.2010.00747.x.
24. Rogers GB, Hoffman LR, Carroll MP, Bruce KD. 2013. Interpreting infective microbiota: the importance of an ecological perspective. Trends Microbiol 21:271–276. http://dx.doi.org/10.1016/j.tim.2013.03.004.
25. Grice EA, Segre JA. 2012. Interaction of the microbiome with the innate immune response in chronic wounds. Adv Exp Med Biol 946:55–68. http://dx.doi.org/10.1007/978-1-4614-0106-3_4.
26. Dhall S, Do D, Garcia M, Wijesinghe DS, Brandon A, Kim J, Sanchez A, Lyubovitsky J, Gallagher S, Nothnagel EA, Chalfant CE, Patel RP, Schiller N, Martins-Green M. 2014. A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity. PLoS One 9:e109848. http://dx.doi.org/10.1371/journal.pone.0109848.
27. Zhao G, Usui ML, Lippman SI, James GA, Stewart PS, Fleckman P, Olerud JE. 2013. Biofilms and inflammation in chronic wounds. Adv Wound Care (New Rochelle) 2:389–399.
28. Edwards R, Harding KG. 2004. Bacteria and wound healing. Curr Opin Infect Dis 17:91–96. http://dx.doi.org/10.1097/00001432-200404000-00004.
29. Wolcott RD, Gontcharova V, Sun Y, Zischakau A, Dowd SE. 2009. Bacterial diversity in surgical site infections: not just aerobic cocci any more. J Wound Care 18:317–323. http://dx.doi.org/10.12968/jowc.2009.18.8.43630.
30. Gardner SE, Frantz RA, Saltzman CL, Hillis SL, Park H, Scherubel M. 2006. Diagnostic validity of three swab techniques for identifying chronic wound infection. Wound Repair Regen 14:548–557. http://dx.doi.org/10.1111/j.1743-6109.2006.00162.x.
31. Cui L, Morris A, Ghedin E. 2013. The human mycobiome in health and disease. Genome Med 5:63. http://dx.doi.org/10.1186/gm467.
32. Findley K, Oh J, Yang J, Conlan S, Deming C, Meyer JA, Schoenfeld D, Nomicos E, Park M, NIH Intramural Sequencing Center Comparative Sequencing Program, Kong HH, Segre JA. 2013. Topographic diversity of fungal and bacterial communities in human skin. Nature 498:367–370. http://dx.doi.org/10.1038/nature12171.
33. Underhill DM, Iliev ID. 2014. The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol 14: 405–416. http://dx.doi.org/10.1038/nri3684.
34. Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, Naqvi A, Gillevet PM. 2010. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog 6:e1000713. http://dx.doi.org/10.1371/journal.ppat.1000713.
35. Di Bonaventura G, Pompilio A, Picciani C, Iezzi M, D’Antonio D, Piccolomini R. 2006. Biofilm formation by the emerging fungal pathogen Trichosporon asahii: development, architecture, and antifungal resistance. Antimicrob Agents Chemother 50:3269–3276. http://dx.doi.org/10.1128/AAC.00556-06.
36. Desai JV, Mitchell AP, Andes DR. 2014. Fungal biofilms, drug resistance, and recurrent infection. Cold Spring Harb Perspect Med 4:a019729. http://dx.doi.org/10.1101/cshperspect.a019729.
37. de Oliveira HC, Assato PA, Marcos CM, Scorzoni L, de Paula E Silva ACA, De Fatima Da Silva J, de Lacorte Singulani J, Alarcon KM, Fusco-Almeida AM, Mendes-Giannini MJS. 2015. Paracoccidioides-host interaction: an overview on recent advances in the paracoccidioidomycosis. Front Microbiol 6:1319. http://dx.doi.org/10.3389/fmicb.2015.01319.
38. Nunes JM, Bizerra FC, Ferreira RCE, Colombo AL. 2013. Molecular identification, antifungal susceptibility profile, and biofilm formation of clinical and environmental Rhodotorula species isolates. Antimicrob Agents Chemother 57:382–389. http://dx.doi.org/10.1128/AAC.01647-12.
39. Kramer R, Sauer-Heilborn A, Welte T, Guzman CA, Abraham W-R, Höfle MG. 2015. Cohort study of airway mycobiome in adult cystic fibrosis patients: differences in community structure between fungi and bacteria reveal predominance of transient fungal elements. J Clin Microbiol 53:2900–2907. http://dx.doi.org/10.1128/JCM.01094-15.
40. Guo R, Zheng N, Lu H, Yin H, Yao J, Chen Y. 2012. Increased diversity of fungal flora in the vagina of patients with recurrent vaginal candidiasis and allergic rhinitis. Microb Ecol 64:918–927. http://dx.doi.org/10.1007/s00248-012-0084-0.
41. Dowd SE, Delton Hanson J, Rees E, Wolcott RD, Zischau AM, Sun Y, White J, Smith DM, Kennedy J, Jones CE. 2011. Survey of fungi and yeast in polymicrobial infections in chronic wounds. J Wound Care 20:40–47. http://dx.doi.org/10.12968/jowc.2011.20.1.40.
42. Chellan G, Shivaprakash S, Karimassery Ramaiyar S, Varma AK, Varma N, Thekkeparambil Sukumaran M, Rohinivilasam Vasukutty J, Bal A, Kumar H. 2010. Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes. J Clin Microbiol 48:2097–2102. http://dx.doi.org/10.1128/JCM.02035-09.
43. Schoch CL, Seifert KA, Huhndorf S, Robert V, Spouge JL, Levesque CA, Chen W, Fungal Barcoding Consortium. 2012. Nuclear ribosomal internal transcribed spacer (ITS) region as a universalDNAbarcode marker for Fungi. Proc Natl Acad Sci U S A 109:6241–6246. http://dx.doi.org/10.1073/pnas.1117018109.
44. Kõljalg U, Nilsson RH, Abarenkov K, Tedersoo L, Taylor AFS, Bahram M, Bates ST, Bruns TD, Bengtsson-Palme J, Callaghan TM, Douglas B, Drenkhan T, Eberhardt U, Dueñas M, Grebenc T, Griffith GW, Hartmann M, Kirk PM, Kohout P, Larsson E, Lindahl BD, Lücking R, Martín MP, Matheny PB, Nguyen NH, Niskanen T, Oja J, Peay KG, Peintner U, Peterson M, Põldmaa K, Saag L, Saar I, Schüßler A, Scott JA, Senés C, Smith ME, Suija A, Taylor DL, Telleria MT, Weiss M, Larsson K-H. 2013. Towards a unified paradigm for sequence-based identification of fungi. Mol Ecol 22:5271–5277. http://dx.doi.org/10.1111/mec.12481.
45. Gweon HS, Oliver A, Taylor J, Booth T, Gibbs M, Read DS, Griffiths RI, Schonrogge K. 2015. PIPITS: an automated pipeline for analyses of fungal internal transcribed spacer sequences from the Illumina sequencing platform. Methods Ecol Evol 6:973–980. http://dx.doi.org/10.1111/2041-210X.12399.
46. Bengtsson-Palme J, Ryberg M, Hartmann M, Branco S, Wang Z, Godhe A, De Wit P, Sánchez-García M, Ebersberger I, de Sousa F, Amend AS, Jumpponen A, Unterseher M, Kristiansson E, Abarenkov K, Bertrand YJK, Sanli K, Eriksson KM, Vik U, Veldre V, Nilsson RH. 2013. Improved software detection and extraction of ITS1 and ITS2 from ribosomal ITS sequences of fungi and other eukaryotes for analysis of environmental sequencing data. Methods Ecol Evol 9:914–919.
47. Wu G, Zhao H, Li C, Rajapakse MP, Wong WC, Xu J, Saunders CW, Reeder NL, Reilman RA, Scheynius A, Sun S, Billmyre BR, Li W, Averette AF, Mieczkowski P, Heitman J, Theelen B, Schröder MS, De Sessions PF, Butler G, Maurer-Stroh S, Boekhout T, Nagarajan N, Dawson TL, Jr. 2015. Genus-wide comparative genomics of Malassezia delineates its phylogeny, physiology, and niche adaptation on human skin. PLoS Genet 11:e1005614. http://dx.doi.org/10.1371/journal.pgen.1005614.
48. Drell T, Lillsaar T, Tummeleht L, Simm J, Aaspõllu A, Väin E, Saarma I, Salumets A, Donders GGG, Metsis M. 2013. Characterization of the vaginal micro- and mycobiome in asymptomatic reproductive-age Estonian women. PLoS One 8:e54379. http://dx.doi.org/10.1371/journal.pone.0054379.
49. Sellart-Altisent M, Torres-Rodríguez JM, Gómez de Ana S, Alvarado- Ramírez E. 2007. Nasal fungal microbiota in allergic and healthy subjects. Rev Iberoam Micol 24:125–130. http://dx.doi.org/10.1016/S1130-1406(07)70027-X.
50. Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, Wu GD, Lewis JD, Bushman FD. 2013. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One 8:e66019. http://dx.doi.org/10.1371/journal.pone.0066019.
51. Smith RM, Schaefer MK, Kainer MA, Wise M, Finks J, Duwve J, Fontaine E, Chu A, Carothers B, Reilly A, Fiedler J, Wiese AD, Feaster C, Gibson L, Griese S, Purfield A, Cleveland AA, Benedict K, Harris JR, Brandt ME, Blau D, Jernigan J, Weber JT, Park BJ. 2013. Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med 369:1598–1609. http://dx.doi.org/10.1056/NEJMoa1213978.
52. Sandoval-Denis M, Sutton DA, Martin-Vicente A, Cano-Lira JF, Wiederhold N, Guarro J, Gené J. 2015. Cladosporium species recovered from clinical samples in the United States. J Clin Microbiol 53:2990–3000. http://dx.doi.org/10.1128/JCM.01482-15.
53. Noverr MC, Huffnagle GB. 2005. The “microflora hypothesis” of allergic diseases. Clin Exp Allergy 35:1511–1520.
54. Forsythe P, Inman MD, Bienenstock J. 2012. Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. Am J Respir Crit Care Med 175:561–569. http://dx.doi.org/10.1164/rccm.200606-821OC.
55. Noverr MC, Noggle RM, Toews GB, Huffnagle GB. 2004. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun 72:4996–5003. http://dx.doi.org/10.1128/IAI.72.9.4996-5003.2004.
56. Noverr MC, Falkowski NR, McDonald RA, McKenzie AN, Huffnagle GB. 2005. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13. Infect Immun 73:30–38. http://dx.doi.org/10.1128/IAI.73.1.30-38.2005.
57. Horner WE, Helbling A, Salvaggio JE, Lehrer SB. 1995. Fungal allergens. Clin Microbiol Rev 8:161–179.
58. Margolis DJ, Berlin JA, Strom BL. 1996. Interobserver agreement, sensitivity, and specificity of a “healed” chronic wound. Wound Repair Regen 4:335–338. http://dx.doi.org/10.1046/j.1524-475X.1996.40309.x.
59. Gardner SE, Frantz RA, Hillis SL, Blodgett TJ, Femino LM, Lehman SM. 2012. Volume measures using a digital image analysis system are reliable in diabetic foot ulcers. Wounds 24:146–151.
60. Dodt M, Roehr JT, Ahmed R, Dieterich C. 2012. FLEXBAR—flexible barcode and adapter processing for next-generation sequencing platforms. Biology 1:895–905. http://dx.doi.org/10.3390/biology1030895.
61. Zhang J, Kobert K, Flouri T, Stamatakis A. 2014. PEAR: a fast and accurate Illumina Paired-End reAd mergeR. Bioinformatics 30:614–620. http://dx.doi.org/10.1093/bioinformatics/btt593.
62. Nilsson RH, Tedersoo L, Ryberg M, Kristiansson E, Hartmann M, Unterseher M, Porter TM, Bengtsson-Palme J, Walker DM, de Sousa F, Gamper HA, Larsson E, Larsson K-H, Kõljalg U, Edgar RC, Abarenkov K. 2015. A comprehensive, automatically updated fungal ITS sequence dataset for reference-based chimera control in environmental sequencing efforts. Microbes Environ 30:145–150. http://dx.doi.org/10.1264/jsme2.ME14121.
63. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R. 2010. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336. http://dx.doi.org/10.1038/nmeth.f.303.
64. R Core Team. 2013. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.`