University of Pittsburgh, Pittsburgh, PA, USA.
J. Craig Venter Institute, La Jolla, CA, 92037, USA.
Nat Commun. 2023 Sep 22;14(1):5918. doi: 10.1038/s41467-023-41509-x.
The longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and -resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.
长期以来的模型认为，大多数血流感染（BSI）是由单一生物体引起的。我们对 10 名念珠菌属 BSIs 患者的每个血液培养（BC）瓶中的 5-10 株进行全基因组测序。我们证明 BC 中含有克隆但遗传上多样化的菌株的混合群体。来自两名患者的遗传上不同的菌株表现出在 BSI 期间可能很重要的表型，包括对抗真菌药物和吞噬作用的敏感性差异。在这两名患者中，临床微生物学实验室都恢复了对氟康唑敏感的指数株，但我们发现了混合的氟康唑敏感和耐药群体。药物敏感性的多样性可能具有临床相关性，因为在持续或复发感染期间，临床实验室随后恢复了氟康唑耐药株。在一名患者中，未被识别的呼吸缺陷小菌落变体对氟康唑耐药，并且在小鼠念珠菌病期间对毒力明显减弱。我们的数据表明，BSI 期间念珠菌属的遗传和表型多样性存在基于群体的模型。
