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Molecular typing of clinical Cryptococcus neoformans isolates collected in Germany from 2004 to 2010

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Abstract

Cryptococcosis is a fungal infection mostly caused by Cryptococcus neoformans. We identified agents of cryptococcosis diagnosed in Germany from 2004 to 2010. We used multi-locus sequence typing (MLST) to understand the molecular epidemiology of cryptococcosis. Sero- and mating types of individual patient isolates were determined by PCR. MLST was performed using the seven-locus scheme. Allele and nucleotide diversity was calculated for each locus of C. neoformans var. grubii and C. neoformans var. neoformans. Phylogenetic relations were assessed by dendrograms. Clinical data were compared between infections caused by the two variants. We studied 101 isolates. Eight were identified as hybrids (8 %). All non-hybrids were of the α mating type. Among 78 C. neoformans var. grubii (77 %), 16 sequence types (STs) were identified including three novel STs. They clustered in four groups, previously isolated in Asia, Europe or worldwide. Among 15 C. neoformans var. neoformans (15 %), 10 STs were identified, without clustering. These isolates showed higher allele, and nucleotide diversity compared with C. neoformans var. grubii. C. neoformans var. neoformans was more likely to cause soft-tissue infections (3/9, 33 vs. 1/63, 2 %, p = 0.005) and to affect non-AIDS patients (7/14, 50 vs. 15/76, 20 %, p = 0.036). C. neoformans var. grubii is the predominant agent of cryptococcosis in Germany. MLST suggests that a part of these cases are acquired abroad by immigrants or tourists. C. neoformans var. neoformans isolates represent a greater genetic diversity and are associated with more variable clinical presentations.

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Acknowledgments

We thank all institutions and physicians providing isolates: Helios Klinikum Heckeshorn Berlin, S.Wagner; Helios Klinikum Buch Berlin; Uniklinik Münster, W. Fegeler; St. Elisabethen KH Frankfurt am Main, J. Bargon; Universität Erlangen, F. Albert; Universität Düsseldorf, Mikrobiologie; Universität Göttingen, U. Groß; Universität Mannheim, H. Hof; Gemeinschaftspraxis Labormedizin Paracelsusstrasse 12, Leverkusen A. Kleiber-Imbeck; Universität Frankfurt am Main, V. Rickerts; Klinikum Chemnitz, ML Kerkmann; Vivantes Klinikum Neukölln; Klinikum Nürnberg, K. Fischer; Universitätsklinik Homburg/Saar; Labor Bertholdt und Kollegen, Frankfurt, Oder; Uniklinik Hannover, Mikrobiologie, L. Sedlacek; Medizinisches Versorgungszentrum Riegel und Partner, Wiesbaden; Laboratorium für Mikrobiologie Mölbis, P. Nenoff; Labor Dr. Gärtner, Ravensburg, T. Schmidt-Wieland; Universität Würzburg Mikrobiologie; Klinikum Traunstein, P. Einring; Universität Mainz, Mikrobiologyie; Med. Versorgungszentrum Dr. Stein und Kollegen, Mönchengladbach, R. Schwarz; Universität Hamburg, Mikrobiologie G. Franke; Krankhenhaus St. Georg, Hamburg, NN; Universität Freiburg, C. Schneider; TU Dresden, Dresden; Städtisches Krankhenhaus Kiel; Uniklinik Heidelberg, Heidelberg; Laborpraxis Osnabrück, Osnabrück; MVZ für Laboratoriumsmedizin Koblenz; Labor Dr. Wittke, Bremen; Klinikum Augsburg; Universität Aachen, G. Haase; Universität Jena, Mikrobiologie. The skilful technical assistance of S. Spodzieja and M. Adam (MVZ Dr. Stein+Kollegen, Mönchengladbach), E. Antweiler, C. Han, H. Losert, W. Pohl, B. Raddatz and M. Seibold is greatly appreciated. The author thanks Aftab Jasir, Androulla Efstratiou and Anton Aebischer for the critical review of the manuscript. We thank Wieland Meyer and Carolina Firacative for the support with the MLST database.

Conflict of interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. Robert Koch-Institut, Nordufer 20, 13353, Berlin, Germany

    Andrea Sanchini, Ilka McCormick Smith, Kathrin Tintelnot & Volker Rickerts

  2. European Public Health Microbiology (EUPHEM) Training Programme, European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden

    Andrea Sanchini

  3. Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany

    Ludwig Sedlacek

  4. MVZ Labor Dr. Stein+Kollegen, Mönchengladbach, Germany

    Roman Schwarz

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  1. Andrea Sanchini
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  2. Ilka McCormick Smith
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Correspondence to Volker Rickerts.

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Sanchini, A., Smith, I.M., Sedlacek, L. et al. Molecular typing of clinical Cryptococcus neoformans isolates collected in Germany from 2004 to 2010. Med Microbiol Immunol 203, 333–340 (2014). https://doi.org/10.1007/s00430-014-0341-6

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