Micrrosus cirrosus SZ 2021: A potentially new genotype of Micrrosus cirrosus, which can cause fatal pulmonary infection in acute leukemia patients after haplo-HSCT

Abstract: Background Uncommon Microascus cirrosus (M.cirrosus) species have been reported to cause growing subcutaneous and invasive fungal infections worldwide. To our knowledge, no comprehensive clinical characteristics and etiological identification in laboratory tests have been defined till now, notably, for fatal pulmonary infections in the crowd of patients undergoing hematopoietic stem cell transplantation (HSCT). Methods We studied the pulmonary infection due to a new M.cirrosus, analyzed other related cases retrospectively in our hospital and reviewed other reported cases. This isolated M.cirrosus was cultured and determined by morphological observation, antifungal susceptibility, multi-locus sequence analysis (MLST), whole genome sequencing, metagenomic next-generation sequencing(mNGS), and other analysis. Results This isolated M.cirrosus named M. cirrosus SZ 2021 was resistant to various therapies and accounted for the fatal pulmonary infection in the HSCT patient. Notably, M.cirrosus could be confirmed by mNGS in another two lung infections of HSCT patients. For this new isolated fungus, it had short chains of conidia without apical cysts for the Micrrosus genus, whereas growing faster and bigger on chocolate agar plate than Sabouraud’s agar. Furthermore, it was not sensitive to fluconazole, amphotericin B, 5-flucytosine, caspofungin and other drugs by drug sensitivity test in vitro, supporting its bad prognosis and a sharp increased colonies across the half month process of insufficient antifungal treatment. This isolate had not been correctly identified until the whole genome sequencing by NGS and MLST were finished, because of the poor knowledge of gene information on the genus. The whole nucleotide sequence (2.693 billion bases) of the genome from M. cirrosus SZ 2021 have been uploaded in NCBI database for the first time. In addition, its protein fingerprint has been presented by MALDI-TOF-MS. Conclusions M. cirrosus SZ 2021 is a potentially new genotype of M.cirrosus, which can cause fatal pulmonary infection in immunocompromised patients. These established complete laboratory tests facilitate its correct and rapid etiological diagnosis, especially for the culture independent rapid detection by mNGS.