AUTHOR=Yu Shu-Ying , Guo Li-Na , Xiao Meng , Zhou Meng-Lan , Yuan Ying , Wang Yao , Zhang Li , Sun Tian-Shu , Ning Ya-Ting , Jia Pei-Yao , Kang Wei , Kong Fanrong , Chen Sharon C.-A. , Zhao Yanan , Xu Ying-Chun 

TITLE=Clinical and Microbiological Characterization of Invasive Pulmonary Aspergillosis Caused by Aspergillus lentulus in China

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01672

DOI=10.3389/fmicb.2020.01672

ISSN=1664-302X

ABSTRACT=<p>Invasive aspergillosis (IA) due to <italic>Aspergillus lentulus</italic> is associated with high mortality. In this study, we investigated the clinical and microbiological characteristics of 6 fatal cases of proven or probable IA caused by <italic>A. lentulus</italic> in China. Underlying immunosuppression, prior antifungal exposure, and intensive care unit (ICU) hospitalization were important risk factors for invasive <italic>A. lentulus</italic> infection. Phenotypic differences were observed for <italic>A. lentulus</italic> isolates including slower growth, reduced sporulation, and inability to grow at 48°C, compared with <italic>Aspergillus fumigatus complex</italic>. ITS sequencing was unable to distinguish <italic>A. lentulus</italic> from <italic>A. fumigatus</italic>, but sequencing of the <italic>benA</italic>, <italic>CaM</italic>, and <italic>rod A</italic> loci enabled reliable distinction of these closely related species. Phylogenetic analysis further confirmed that the ITS region had little variation within the <italic>Aspergillus</italic> section Fumigati while the <italic>benA</italic> gene offered the highest intraspecific discrimination. Microsatellite typing results revealed that only loci on chromosomes 1, 3, 5, and 6b generated detectable amplicons for identification. All <italic>A. lentulus</italic> isolates showed <italic>in vitro</italic> resistance to multiple antifungal drugs including amphotericin B (MIC range 4 to 8 μg/ml), itraconazole (MIC 2 μg/ml), voriconazole (MIC of 4–16 μg/ml), and posaconazole (MIC of 0.5–1 μg/ml). However, MECs for the echinocandin drugs ranged from 0.03–0.25, ≤0.008–0.015, and ≤0.015–0.03 μg/ml for caspofungin, micafungin, and anidulafungin, respectively. <italic>A. lentulus</italic> is an emerging fungal pathogen in China, causing fatal disease, and clinicians as well as laboratories should be alert to their increasing presence.</p>