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Abstract

Mucormycoses are invasive infections by species and other Mucorales. Over 10 months, four solid organ transplant (SOT) recipients at our centre developed mucormycosis due to (=2), (=1) or (=1), at a median 31.5 days (range: 13–34) post-admission. We performed whole genome sequencing (WGS) on 72 Mucorales isolates (45 . , 19 . , six . , two species) from these patients, from five patients with community-acquired mucormycosis, and from hospital and regional environments. Isolates were compared by core protein phylogeny and global genomic features, including genome size, guanine–cytosine percentages, shared protein families and paralogue expansions. Patient isolates fell into six core phylogenetic lineages (clades). Phylogenetic and genomic similarities of isolates recovered 7 months apart from two SOT recipients in adjoining hospitals suggested a potential common source exposure. However, isolates from other patients and environmental sites had unique genomes. Many isolates that were indistinguishable by core phylogeny were distinct by one or more global genomic comparisons. Certain clades were recovered throughout the study period, whereas others were found at particular time points. In conclusion, mucormycosis cases could not be genetically linked to a definitive environmental source. Comprehensive genomic analyses eliminated false associations between Mucorales isolates that would have been assigned using core phylogenetic or less extensive genomic comparisons. The genomic diversity of Mucorales mandates that multiple isolates from individual patients and environmental sites undergo WGS during epidemiological investigations. However, exhaustive surveillance of fungal populations in a hospital and surrounding community is probably infeasible.

Funding
This study was supported by the:
  • Medical Center, University of Pittsburgh
    • Principle Award Recipient: M. Hong Nguyen
  • National Science Foundation (Award OCE-1259994)
    • Principle Award Recipient: Christopher L. Dupont
  • National Science Foundation (Award IOS-1354423)
    • Principle Award Recipient: Christopher L. Dupont
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2020-11-27
2024-04-19
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References

  1. Davoudi S, Graviss LS, Kontoyiannis DP. Healthcare-associated outbreaks due to mucorales and other uncommon fungi. Eur J Clin Invest 2015; 45:767–773 [View Article][PubMed]
    [Google Scholar]
  2. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41:634–653 [View Article][PubMed]
    [Google Scholar]
  3. Ibrahim AS, Edwards JE, Bryant R, Spellberg B. Economic burden of mucormycosis in the United States: can a vaccine be cost-effective?. Med Mycol 2009; 47:592–600 [View Article][PubMed]
    [Google Scholar]
  4. Antoniadou A. Outbreaks of zygomycosis in hospitals. Clin Microbiol Infect 2009; 15 Suppl 5:55–59 [View Article][PubMed]
    [Google Scholar]
  5. Cheng VCC, Chen JHK, Wong SCY, Leung SSM, So SYC et al. Hospital outbreak of pulmonary and cutaneous zygomycosis due to contaminated linen items from substandard laundry. Clin Infect Dis 2016; 62:714–721 [View Article][PubMed]
    [Google Scholar]
  6. Duffy J, Harris J, Gade L, Sehulster L, Newhouse E et al. Mucormycosis outbreak associated with hospital linens. Pediatr Infect Dis J 2014; 33:472–476 [View Article][PubMed]
    [Google Scholar]
  7. El-Mahallawy HA, Khedr R, Taha H, Shalaby L, Mostafa A. Investigation and management of a Rhizomucor outbreak in a pediatric cancer hospital in Egypt. Pediatr Blood Cancer 2016; 63:171–173 [View Article][PubMed]
    [Google Scholar]
  8. Maraví-Poma E, Rodríguez-Tudela JL, de Jalón JG, Manrique-Larralde A, Torroba L et al. Outbreak of gastric mucormycosis associated with the use of wooden tongue depressors in critically ill patients. Intensive Care Med 2004; 30:724–728 [View Article][PubMed]
    [Google Scholar]
  9. Mitchell SJ, Gray J, Morgan ME, Hocking MD, Durbin GM. Nosocomial infection with Rhizopus microsporus in preterm infants: association with wooden tongue depressors. Lancet 1996; 348:441–443 [View Article][PubMed]
    [Google Scholar]
  10. Novosad SA, Vasquez AM, Nambiar A, Arduino MJ, Christensen E et al. Notes from the field: Probable mucormycosis among adult solid organ transplant recipients at an acute care hospital - pennsylvania, 2014-2015. MMWR Morb Mortal Wkly Rep 2016; 65:481–482 [View Article][PubMed]
    [Google Scholar]
  11. Rammaert B, Lanternier F, Zahar J-R, Dannaoui E, Bougnoux M-E et al. Healthcare-Associated mucormycosis. Clin Infect Dis 2012; 54 Suppl 1:S44–S54 [View Article][PubMed]
    [Google Scholar]
  12. Teal LJ, Schultz KM, Weber DJ, Gergen MF, Miller MB et al. Invasive cutaneous Rhizopus infections in an immunocompromised patient population associated with Hospital laundry CARTS. Infect Control Hosp Epidemiol 2016; 37:1251–1253 [View Article][PubMed]
    [Google Scholar]
  13. Verweij PE, Voss A, Donnelly JP, de Pauw BE, Meis JF. Wooden sticks as the source of a pseudoepidemic of infection with Rhizopus microsporus var. rhizopodiformis among immunocompromised patients. J Clin Microbiol 1997; 35:2422–2423 [View Article][PubMed]
    [Google Scholar]
  14. Llata E, Blossom DB, Khoury HJ, Rao CY, Wannemuehler KA et al. A cluster of mucormycosis infections in hematology patients: challenges in investigation and control of invasive mold infections in high-risk patient populations. Diagn Microbiol Infect Dis 2011; 71:72–80 [View Article][PubMed]
    [Google Scholar]
  15. Lalayanni C, Baliakas P, Xochelli A, Apostolou C, Arabatzis M et al. Outbreak of cutaneous zygomycosis associated with the use of adhesive tape in haematology patients. J Hosp Infect 2012; 81:213–215 [View Article][PubMed]
    [Google Scholar]
  16. Garner D, Machin K. Investigation and management of an outbreak of mucormycosis in a paediatric oncology unit. J Hosp Infect 2008; 70:53–59 [View Article][PubMed]
    [Google Scholar]
  17. LeMaile-Williams M, Burwell LA, Salisbury D, Noble-Wang J, Arduino M et al. Outbreak of cutaneous Rhizopus arrhizus infection associated with karaya ostomy bags. Clin Infect Dis 2006; 43:e83–e88 [View Article][PubMed]
    [Google Scholar]
  18. Christiaens G, Hayette MP, Jacquemin D, Melin P, Mutsers J et al. An outbreak of Absidia corymbifera infection associated with bandage contamination in a burns unit. J Hosp Infect 2005; 61:88 [View Article][PubMed]
    [Google Scholar]
  19. Abzug MJ, Gardner S, Glode MP, Cymanski M, Roe MH et al. Heliport-associated nosocomial mucormycoses. Infect Control Hosp Epidemiol 1992; 13:325–326 [View Article][PubMed]
    [Google Scholar]
  20. Hartnett KP, Jackson BR, Perkins KM, Glowicz J, Kerins JL et al. A guide to investigating suspected outbreaks of mucormycosis in healthcare. J Fungi 2019; 5:E6969 24 Jul 2019 [View Article][PubMed]
    [Google Scholar]
  21. Nagao K, Ota T, Tanikawa A, Takae Y, Mori T et al. Genetic identification and detection of human pathogenic Rhizopus species, a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene. J Dermatol Sci 2005; 39:23–31 [View Article][PubMed]
    [Google Scholar]
  22. Cendejas-Bueno E, Kolecka A, Alastruey-Izquierdo A, Theelen B, Groenewald M et al. Reclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group i), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts. J Clin Microbiol 2012; 50:3641–3651 [View Article][PubMed]
    [Google Scholar]
  23. Gryganskyi AP, Golan J, Dolatabadi S, Mondo S, Robb S et al. Phylogenetic and phylogenomic definition of Rhizopus species. G3 2018; 8:2007–2018 [View Article]
    [Google Scholar]
  24. Neblett Fanfair R, Benedict K, Bos J, Bennett SD, Lo Y-C et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med 2012; 367:2214–2225 [View Article][PubMed]
    [Google Scholar]
  25. Garcia-Hermoso D, Criscuolo A, Lee SC, Legrand M, Chaouat M et al. Outbreak of invasive wound mucormycosis in a burn unit due to multiple strains of mucor circinelloides F. Circinelloides resolved by whole-genome sequencing. mBio 2018; 9:e00573-18 24 04 2018 [View Article][PubMed]
    [Google Scholar]
  26. Marek C, Croxen MA, Dingle TC, Bharat A, Schwartz IS et al. The use of genome sequencing to investigate an outbreak of hospital-acquired mucormycosis in transplant patients. Transpl Infect Dis 2019; 21:e13163 [View Article][PubMed]
    [Google Scholar]
  27. Etienne KA, Gillece J, Hilsabeck R, Schupp JM, Colman R et al. Whole genome sequence typing to investigate the Apophysomyces outbreak following a tornado in Joplin, Missouri, 2011. PLoS One 2012; 7:e49989 [View Article][PubMed]
    [Google Scholar]
  28. Chibucos MC, Soliman S, Gebremariam T, Lee H, Daugherty S et al. An integrated genomic and transcriptomic survey of mucormycosis-causing fungi. Nat Commun 2016; 7:12218 [View Article][PubMed]
    [Google Scholar]
  29. Spellberg B, Andes D, Perez M, Anglim A, Bonilla H et al. Safety and outcomes of open-label deferasirox iron chelation therapy for mucormycosis. Antimicrob Agents Chemother 2009; 53:3122–3125 [View Article][PubMed]
    [Google Scholar]
  30. Lee SC, Billmyre RB, Li A, Carson S, Sykes SM et al. Analysis of a food-borne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt. mBio 2014; 5:e01390–01314 [View Article][PubMed]
    [Google Scholar]
  31. Zhou P, Zhang G, Chen S, Jiang Z, Tang Y et al. Genome sequence and transcriptome analyses of the thermophilic zygomycete fungus Rhizomucor miehei . BMC Genomics 2014; 15:294 [View Article][PubMed]
    [Google Scholar]
  32. Sundermann AJ, Clancy CJ, Pasculle AW, Liu G, Cumbie RB et al. How clean is the linen at my hospital? the Mucorales on unclean linen discovery study of large United States transplant and cancer centers. Clinical Infectious Diseases 2018ciy669
    [Google Scholar]
  33. van Burik JA, Schreckhise RW, White TC, Bowden RA, Myerson D. Comparison of six extraction techniques for isolation of DNA from filamentous fungi. Med Mycol 1998; 36:299–303 [View Article][PubMed]
    [Google Scholar]
  34. Nyaga MM, Tan Y, Seheri ML, Halpin RA, Akopov A et al. Whole-genome sequencing and analyses identify high genetic heterogeneity, diversity and endemicity of rotavirus genotype P[6] strains circulating in Africa. Infect Genet Evol 2018; 63:79–88 [View Article][PubMed]
    [Google Scholar]
  35. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article][PubMed]
    [Google Scholar]
  36. Simão FA, Waterhouse RM, Ioannidis P, Kriventseva EV, Zdobnov EM. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics 2015; 31:3210–3212 [View Article][PubMed]
    [Google Scholar]
  37. Stanke M, Keller O, Gunduz I, Hayes A, Waack S et al. Augustus: ab initio prediction of alternative transcripts. Nucleic Acids Res 2006; 34:W435–W439 [View Article][PubMed]
    [Google Scholar]
  38. Cantarel BL, Korf I, Robb SMC, Parra G, Ross E et al. Maker: an easy-to-use annotation pipeline designed for emerging model organism genomes. Genome Res 2008; 18:188–196 [View Article][PubMed]
    [Google Scholar]
  39. Darling AE, Jospin G, Lowe E, Matsen FA, Bik HM et al. PhyloSift: phylogenetic analysis of genomes and metagenomes. PeerJ 2014; 2:e243 [View Article][PubMed]
    [Google Scholar]
  40. Sievers F, Higgins DG. Clustal omega for making accurate alignments of many protein sequences. Protein Sci 2018; 27:135–145 [View Article][PubMed]
    [Google Scholar]
  41. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014; 30:1312–1313 [View Article][PubMed]
    [Google Scholar]
  42. Stamatakis A. Using RAxML to infer phylogenies. Curr Protoc Bioinformatics 2015; 51:11–14 [View Article]
    [Google Scholar]
  43. Fouts DE, Brinkac L, Beck E, Inman J, Sutton G. PanOCT: automated clustering of orthologs using conserved gene neighborhood for pan-genomic analysis of bacterial strains and closely related species. Nucleic Acids Res 2012; 40:e172 [View Article][PubMed]
    [Google Scholar]
  44. Chitsaz H, Yee-Greenbaum JL, Tesler G, Lombardo M-J, Dupont CL et al. Efficient de novo assembly of single-cell bacterial genomes from short-read data sets. Nat Biotechnol 2011; 29:915–921 [View Article]
    [Google Scholar]
  45. Chaves MS, Leonardelli F, Franco DM, Ríos PG, Colli GM et al. Control of an outbreak of post-transplant cutaneous mucormycosis by removing the vehicle: an intervention study of contiguous cohorts. Am J Infect Control
    [Google Scholar]
  46. Chazalet V, Debeaupuis JP, Sarfati J, Lortholary J, Ribaud P et al. Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings. J Clin Microbiol 1998; 36:1494–1500 [View Article][PubMed]
    [Google Scholar]
  47. Debeaupuis JP, Sarfati J, Chazalet V, Latgé JP. Genetic diversity among clinical and environmental isolates of Aspergillus fumigatus . Infect Immun 1997; 65:3080–3085 [View Article][PubMed]
    [Google Scholar]
  48. Sivagnanam S, Sengupta DJ, Hoogestraat D, Jain R, Stednick Z et al. Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic malignancies at a large comprehensive cancer center. Antimicrob Resist Infect Control 2017; 6:123 [View Article][PubMed]
    [Google Scholar]
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