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These two species of <jats:italic>Cryptococcus<\/jats:italic> have differences in pathogenicity, diagnosis, and treatment. Cryptococcal infections are usually difficult to identify because of their slow growth in vitro. In addition, the long detection cycle of <jats:italic>Cryptococcus<\/jats:italic> in clinical specimens makes the diagnosis of Cryptococcal infections difficult. Here, we used positively charged silver nanoparticles (AgNPs<jats:sup>+<\/jats:sup>) as a substrate to distinguish between <jats:italic>C. neoformans<\/jats:italic> and <jats:italic>C. gattii<\/jats:italic> in clinical specimens directly via surface-enhanced Raman scattering (SERS) and spectral analysis. The AgNPs<jats:sup>+<\/jats:sup> self-assembled on the surface of the fungal cell wall via electrostatic aggregation, leading to enhanced SERS signals that were better than the standard substrate negatively charged silver nanoparticles (AgNPs). The SERS spectra could also be used as a sample database in the multivariate analysis via orthogonal partial least-squares discriminant analysis. This novel SERS detection method can clearly distinguish between the two Cryptococcus species using principal component analysis. The accuracy of the training data and test data was 100% after a tenfold crossover validation.<\/jats:p>","DOI":"10.1038\/s41598-020-68978-0","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T06:03:22Z","timestamp":1595829802000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A novel method for identifying and distinguishing Cryptococcus neoformans and Cryptococcus gattii by surface-enhanced Raman scattering using positively charged silver nanoparticles"],"prefix":"10.1038","volume":"10","author":[{"given":"Shan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"68978_CR1","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nrmicro.2015.6","volume":"14","author":"RC May","year":"2016","unstructured":"May, R. 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