1887

Abstract

In 2018, a cluster of two cases of cryptococcosis occurred at the Queen Elizabeth University Hospital (QEUH) in Glasgow, Scotland (UK). It was postulated that these cases may have been linked to pigeon droppings found on the hospital site, given there have been previous reports of associated with pigeon guano. Although some samples of pigeon guano taken from the site yielded culturable yeast from genera related to , they have since been classified as or spp., and no isolates of were recovered from either the guano or subsequent widespread air sampling. In an attempt to further elucidate any possible shared source of the clinical isolates, we used whole-genome sequencing and phylogenetic analysis to examine the relationship of the two isolates from the QEUH cases, along with two isolates from sporadic cases treated at a different Glasgow hospital earlier in 2018. Our work demonstrated that these four clinical isolates were not clonally related; while all isolates were from the VNI global lineage and of the same mating type (MATα), the genotypes of the two QEUH isolates were separated by 1885 base changes and belonged to different sub-lineages, recently described as the intercontinental sub-clades VNIa-93 and VNIa-5. In contrast, one of the two sporadic 2018 clinical isolates was determined to belong to the VNIb sub-lineage and the other classified as a VNIV/VNI hybrid. Our work demonstrated that the two 2018 QEUH isolates and the two prior clinical isolates were all genetically distinct. It was not possible to determine whether the QEUH genotypes stemmed from independent sources or from the same source, i.e. pigeons carrying different genotypes, but it should be noted that whilst members of allied genera within the were isolated from the hospital environment, there were no environmental isolations of .

Funding
This study was supported by the:
  • MatthewC Fisher , Medical Research Council , (Award MR/R015600/1)
  • RhysA Farrer , Wellcome Trust (GB) , (Award 215239/Z/19/Z)
  • ChristinaA Cuomo , National Institute of Allergy and Infectious Diseases , (Award U19AI110818)
  • RhysA Farrer , Medical Research Council , (Award MR/N006364/2)
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000537
2021-02-23
2021-02-27
Loading full text...

Full text loading...

/deliver/fulltext/mgen/10.1099/mgen.0.000537/mgen000537.html?itemId=/content/journal/mgen/10.1099/mgen.0.000537&mimeType=html&fmt=ahah

References

  1. Coelho C, Farrer RA. Pathogen and host genetics underpinning cryptococcal disease. Adv Genet 2020; 105: 1 66 [CrossRef] [PubMed]
    [Google Scholar]
  2. Mattsson R, Haemig PD, Olsen B. Feral pigeons as carriers of Cryptococcus laurentii, Cryptococcus uniguttulatus and Debaryomyces hansenii . Med Mycol 1999; 37: 367 369 [CrossRef]
    [Google Scholar]
  3. Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17: 873 881 [CrossRef]
    [Google Scholar]
  4. Nielsen K, De Obaldia AL, Heitman J. Cryptococcus neoformans mates on pigeon guano: implications for the realized ecological niche and globalization. Eukaryot Cell 2007; 6: 949 959 [CrossRef]
    [Google Scholar]
  5. Isfahani BN, Shadzi SH, Chadegani Pour M, Ilchi N. Isolation and detection of Cryptococcus neoformans from pigeon droppings: Isfahan and it’s suburbs province pigeon towers. J Res Med Sci 2001; 6: 3458
    [Google Scholar]
  6. Refai M, Taha M, Selim SA, Elshabourii F, Yousseff HH. Isolation of Cryptococcus neoformans, Candida albicans and other yeasts from pigeon droppings in Egypt. Sabouraudia 1983; 21: 163 165 [CrossRef] [PubMed]
    [Google Scholar]
  7. Iowa State University Center for Food Security and Public Health Cryptococcosis. Center for Food Security and Public Health Tech Factsheets 45 Ames, IA: Iowa State University; 2013
    [Google Scholar]
  8. Dromer F, Casadevall A, Perfect J, Sorrell T. Cryptococcus neoformans: latency and disease. Cryptococcus: from Human Pathogen to Model Yeast New York: Wiley; 2010 pp 429 439
    [Google Scholar]
  9. Garcia-Hermoso D, Janbon G, Dromer F. Epidemiological evidence for dormant Cryptococcus neoformans infection. J Clin Microbiol 1999; 37: 3204 3209 [CrossRef] [PubMed]
    [Google Scholar]
  10. Alanio A. Dormancy in Cryptococcus neoformans: 60 years of accumulating evidence. J Clin Invest 2020; 130: 3353 3360 [CrossRef]
    [Google Scholar]
  11. Janbon G, Ormerod KL, Paulet D, Byrnes EJ, Yadav V et al. Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLoS Genet 2014; 10: e1004261 [CrossRef]
    [Google Scholar]
  12. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv 2013 1303.3997 (q-bio.GN)
    [Google Scholar]
  13. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25: 2078 2079 [CrossRef]
    [Google Scholar]
  14. Desjardins CA, Giamberardino C, Sykes SM, Yu C-H, Tenor JL et al. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans . Genome Res 2017; 27: 1207 1219 [CrossRef]
    [Google Scholar]
  15. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010; 20: 1297 1303 [CrossRef]
    [Google Scholar]
  16. Danecek P, Auton A, Abecasis G, Albers CA, Banks E et al. The variant call format and VCFtools. Bioinformatics 2011; 27: 2156 2158 [CrossRef]
    [Google Scholar]
  17. Price MN, Dehal PS, Arkin AP. FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 2009; 26: 1641 1650 [CrossRef]
    [Google Scholar]
  18. Abraham G, Inouye M. Fast principal component analysis of large-scale genome-wide data. PLoS One 9: e93766 [CrossRef]
    [Google Scholar]
  19. BBC News Two dead after pigeon dropping infection. BBC News, 19 January 2019 ( https://www.bbc.com/news/uk-scotland-glasgow-west-46931028); . 2019
  20. Ashton PM, Thanh LT, Trieu PH, Van Anh D, Trinh NM et al. Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans . Nat Commun 2019; 10: 2035 10 [CrossRef]
    [Google Scholar]
  21. Litvintseva AP, Carbone I, Rossouw J, Thakur R, Govender NP et al. Evidence that the human pathogenic fungus Cryptococcus neoformans var. grubii may have evolved in Africa. PLoS One 2011; 6: e19688 [CrossRef]
    [Google Scholar]
  22. Litvintseva AP, Marra RE, Nielsen K, Heitman J, Vilgalys R et al. Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in sub-Saharan Africa. Eukaryot Cell 2003; 2: 1162 1168 [CrossRef]
    [Google Scholar]
  23. Rhodes J, Desjardins CA, Sykes SM, Beale MA, Vanhove M et al. Tracing genetic exchange and biogeography of Cryptococcus neoformans var. grubii at the global population level. Genetics 2017; 207: 327 346 [CrossRef]
    [Google Scholar]
  24. Sionov E, Lee H, Chang YC, Kwon-Chung KJ. Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS Pathog 2010; 6: e1000848 [CrossRef]
    [Google Scholar]
  25. Vallabhaneni S, Haselow D, Lloyd S, Lockhart S, Moulton-Meissner H et al. Cluster of Cryptococcus neoformans infections in intensive care unit, Arkansas, USA, 2013. Emerg Infect Dis 2015; 21: 1719 1724 [CrossRef]
    [Google Scholar]
  26. Currie BP, Freundlich LF, Casadevall A. Restriction fragment length polymorphism analysis of Cryptococcus neoformans isolates from environmental (pigeon excreta) and clinical sources in New York City. J Clin Microbiol 1994; 32: 1188 1192 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000537
Loading
/content/journal/mgen/10.1099/mgen.0.000537
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error