APPLIED MICROBIAL AND CELL PHYSIOLOGY Murine model to follow hyphal development in invasive pulmonary aspergillosis Zsuzsa M. Szigeti 1 & Laszlo Talas 1 & Zoltan Palicz 2 & Peter Szentesi 2 & Zoltan Hargitai 3 & Laszlo Csernoch 2 & Jozsef Balla 4 & Istvan Pocsi 1 & Gaspar Banfalvi 1 & Gabor Szeman-Nagy 1 Received: 15 November 2017 /Revised: 17 January 2018 /Accepted: 18 January 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Aspergillus fumigatus is an opportunistic pathogen, the leading cause of invasive and disseminated aspergillosis in systemic immunocompromised patients, and an important cause of mortality. The aim of the present study was to adapt a pulmonary aspergillosis murine model, to determine pathodynamical parameters quantitatively, and to follow the progression of fungal infection in vivo. The nasal inoculation of Aspergillus conidia in mice previously subjected to immunosuppression with cyclo- phosphamide (CP) turned out to be a more suitable model than that of immunosuppressed with hydrocortisone (HC). The following parameters were found to correlate quantitatively with the progress of the infection: (i) survival rate, (ii) weight loss of mice, (iii) infected focal plaque size, (iv) hyphal density, (v) hyphal length distribution of A. fumigatus, and the (vi) the histopathological status and scores. These parameters will be essential elements for the development of antifungal drugs and therapies, and important for the investigation of the pathogenicity in different strains of A. fumigatus. Keywords Aspergillus fumigatus . Conidia . Hyphal outgrowth . Pulmonary aspergillosis . Histological examination Introduction Aspergillus fumigatus may cause invasive aspergillosis in sys- temic immunocompromised, organ-transplanted, and in can- cer patients with high mortality (Aslam et al. 1971). Challenges and solutions of invasive aspergillosis have been recently reviewed (Bassetti et al. 2017). Recent global esti- mates have found that fungal diseases affect over 1 billion people, among them three million cases of chronic pulmonary aspergillosis (Bongomin et al. 2017). The incidence of inva- sive aspergillosis cases is increasing along with the growing number of immunocompromised patients. Besides the rising number of cases, it remains a challenging task that early diag- nosis does not improve significantly the status of patients. The most often used galactomannan and β-D-glucan assays that detect cell wall antigens of Aspergillus are not quite reliable and seem to depend too much on clinicians’ judgment (Johnson et al. 2014; Cadena et al. 2016). The broad aspects of medical profession and clinical judgments are contrasted by the rise of modern research methodology. Specific approaches do not exclude panfungal screening of invasive fungal infec- tions such as bronchoalveolar lavage (BAL) with PCR- ELISA, pan-ACF, pan-PCR, etc. (Trubiano et al. 2016). To improve the efficacy of the antifungal activity of the growing number of new antifungal agents and their combina- tions against invasive pulmonary aspergillosis also necessitat- ed to define the exact parameters of reliable tests of aspergil- losis. Among the most often investigated parameters of asper- gillosis are changes in body weight, mortality, histopathology (Dennis et al. 2006), galactomannan level in the blood (Balloy et al. 2005; Carroll et al. 2016), chitin assay (Balloy et al. 2005), and judgment of fungal burden (Dennis et al. 2006). Gaspar Banfalvi and Gabor Szeman-Nagy contributed equally to this work. * Gaspar Banfalvi gaspar.banfalvi@gmail.com 1 Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, 1 Egyetem Square, Debrecen H-4002, Hungary 2 Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen H-4002, Hungary 3 Department of Pathology, Kenezy Hospital, University of Debrecen, Debrecen H-4031, Hungary 4 Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4002, Hungary Applied Microbiology and Biotechnology https://doi.org/10.1007/s00253-018-8800-4