Bertout Sébastien, Laroche Laetitia, Roger Frédéric, Krasteva Donika, Drakulovski Pascal, Bellet Virginie
Laboratoire de Parasitologie et Mycologie Médicale, TransVIHMI, University of Montpellier, INSERM, IRD, 15 Avenue Charles Flahaut, 34093 Montpellier, France.
Laboratoire de Biologie Médicale, Hôpital Lozère, 48000 Mende, France.
Pathogens. 2023 May 24;12(6):758. doi: 10.3390/pathogens12060758.
Neuromeningeal cryptococcosis is a life-threatening infection of the central nervous system, caused by encapsulated yeast belonging to the and species complexes. Recent data showed that virulence and antifungal resistance are variable for yeasts belonging to the species complex. There is an increase in resistance to fluconazole for yeasts of the species complex and the virulence is variable according to the genotype. In the present study, (i) we explored and compared the mechanisms of resistance to fluconazole between clinically resistant strains and induced fluconazole-resistant strains by exposure to fluconazole in vitro, and (ii) we studied their virulence in the study model. We demonstrated that the fluconazole resistance mechanisms involved were different between clinically resistant strains and induced resistant strains. We also demonstrated that fluconazole-induced resistant strains are less virulent when compared to the original susceptible strains. On the contrary, the clinically resistant strain tested maintains its virulence compared to fluconazole-susceptible strains of the same sequence type.
神经脑膜隐球菌病是一种由新型隐球菌复合体和格特隐球菌复合体中的包膜酵母菌引起的危及生命的中枢神经系统感染。最近的数据表明，新型隐球菌复合体中的酵母菌毒力和抗真菌耐药性存在差异。格特隐球菌复合体中的酵母菌对氟康唑的耐药性增加，且毒力因基因型而异。在本研究中，（i）我们探索并比较了临床耐药菌株与体外暴露于氟康唑诱导的氟康唑耐药菌株之间对氟康唑的耐药机制，（ii）我们在研究模型中研究了它们的毒力。我们证明，临床耐药菌株和诱导耐药菌株所涉及的氟康唑耐药机制不同。我们还证明，与原始敏感菌株相比，氟康唑诱导的耐药菌株毒力较低。相反，与相同序列类型的氟康唑敏感菌株相比，所测试的临床耐药菌株保持其毒力。
