Szweda Piotr, Gucwa Katarzyna, Romanowska Ewa, Dzierz Anowska-Fangrat Katarzyna, Naumiuk Łukasz, Brillowska-Da Browska Anna, Wojciechowska-Koszko Iwona, Milewski Sławomir
Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdansk, Poland.
Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland.
J Med Microbiol. 2015 Jun;64(6):610-619. doi: 10.1099/jmm.0.000062. Epub 2015 Mar 27.
Candida glabrata is currently ranked as the second most frequently isolated aetiological agent of human fungal infections, next only to Candida albicans. In comparison with C. albicans, C. glabrata shows lower susceptibility to azoles, the most common agents used in treatment of fungal infections. Interestingly, the mechanisms of resistance to azole agents in C. albicans have been much better investigated than those in C. glabrata. The aim of the presented study was to determine the mechanisms of resistance to azoles in 81 C. glabrata clinical isolates from three different hospitals in Poland. The investigation was carried out with a Sensititre Yeast One test and revealed that 18 strains were resistant to fluconazole, and 15 were cross-resistant to all other azoles tested (voriconazole, posaconazole and itraconazole). One isolate resistant to fluconazole was cross-resistant to voriconazole, and resistance to voriconazole only was observed in six other isolates. All strains were found to be susceptible to echinocandins and amphotericin B, and five were classified as resistant to 5-fluorocytosine. The sequence of the ERG11 gene encoding lanosterol 14-α demethylase (the molecular target of azoles) of 41 isolates, including all strains resistant to fluconazole and three resistant only to voriconazole, was determined, and no amino acid substitutions were found. Real-time PCR studies revealed that 13 of 15 azole-resistant strains showed upregulation of the CDR1 gene encoding the efflux pump. No upregulation of expression of the CDR2 or ERG11 gene was observed.
光滑念珠菌目前被列为人类真菌感染中第二常见的病原体，仅次于白色念珠菌。与白色念珠菌相比，光滑念珠菌对唑类药物（治疗真菌感染最常用的药物）的敏感性较低。有趣的是，白色念珠菌对唑类药物的耐药机制比光滑念珠菌的研究更为深入。本研究的目的是确定来自波兰三家不同医院的81株光滑念珠菌临床分离株对唑类药物的耐药机制。采用Sensititre Yeast One试验进行研究，结果显示18株菌株对氟康唑耐药，15株对所有其他测试的唑类药物（伏立康唑、泊沙康唑和伊曲康唑）交叉耐药。一株对氟康唑耐药的分离株对伏立康唑交叉耐药，另外六株分离株仅对伏立康唑耐药。所有菌株对棘白菌素和两性霉素B敏感，五株对5-氟胞嘧啶耐药。测定了41株分离株（包括所有对氟康唑耐药的菌株和三株仅对伏立康唑耐药的菌株）编码羊毛甾醇14-α脱甲基酶（唑类药物的分子靶点）的ERG11基因序列，未发现氨基酸替代。实时PCR研究显示，15株唑类耐药菌株中有13株编码外排泵的CDR1基因上调。未观察到CDR2或ERG11基因表达上调。
