Department of Pharmacy, Singapore General Hospital, Blk 8 Level 2, Outram Road, Singapore, 169608, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-01, Singapore, 117549, Singapore.
BMC Infect Dis. 2019 Jan 17;19(1):63. doi: 10.1186/s12879-019-3672-5.
Antifungal resistance rates are increasing. We investigated the mechanisms of azole resistance of Candida spp. bloodstream isolates obtained from a surveillance study conducted between 2012 and 2015.
Twenty-six azole non-susceptible Candida spp. clinical isolates were investigated. Antifungal susceptibilities were determined using the Sensititre YeastOne® YO10 panel. The ERG11 gene was amplified and sequenced to identify amino acid polymorphisms, while real-time PCR was utilised to investigate the expression levels of ERG11, CDR1, CDR2 and MDR1.
Azole cross-resistance was detected in all except two isolates. Amino acid substitutions (A114S, Y257H, E266D, and V488I) were observed in all four C. albicans tested. Of the 17 C. tropicalis isolates, eight (47%) had ERG11 substitutions, of which concurrent observation of Y132F and S154F was the most common. A novel substitution (I166S) was detected in two of the five C. glabrata isolates. Expression levels of the various genes differed between the species but CDR1 and CDR2 overexpression appeared to be more prominent in C. glabrata.
There was interplay of various different mechanisms, including mechanisms which were not studied here, responsible for azole resistance in Candida spp in our study.
抗真菌药物耐药率正在上升。我们研究了 2012 年至 2015 年进行的一项监测研究中获得的血流感染念珠菌属分离株的唑类耐药机制。
研究了 26 株唑类药物不敏感的念珠菌属临床分离株。使用 Sensititre YeastOne® YO10 药敏板来确定抗真菌药物敏感性。扩增和测序 ERG11 基因以鉴定氨基酸多态性，同时利用实时 PCR 来研究 ERG11、CDR1、CDR2 和 MDR1 的表达水平。
除了两个分离株之外，所有分离株都检测到唑类交叉耐药。在所有测试的 4 株白色念珠菌中都观察到氨基酸取代（A114S、Y257H、E266D 和 V488I）。在 17 株热带念珠菌中，有 8 株（47%）存在 ERG11 取代，其中最常见的是同时观察到 Y132F 和 S154F。在 5 株光滑念珠菌中，有 2 株检测到一个新的取代（I166S）。不同种属之间各基因的表达水平不同，但似乎在光滑念珠菌中 CDR1 和 CDR2 的过度表达更为突出。
在我们的研究中，各种不同的机制相互作用，包括这里未研究的机制，导致了念珠菌属对唑类药物的耐药。
