Institute of Medical Sciences (IMS), University of Aberdeen, Aberdeen, United Kingdom.
MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom.
PLoS Pathog. 2024 Mar 11;20(3):e1012076. doi: 10.1371/journal.ppat.1012076. eCollection 2024 Mar.
Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in some infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C. auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host.
耳念珠菌是一种对人类有致病性的真菌病原体，可导致医院获得性感染，死亡率很高。其对抗真菌药物的高度耐药性和在环境中的持久性意味着这些感染很难治疗和从医疗环境中根除。了解这种真菌的生命周期和遗传学，是理解其与临床相关特征（如抗真菌耐药性和毒力）的基础，对于开发新的治疗方法和疗法至关重要。流行病学和基因组研究已经确定了五个地理分支（I-V），它们显示出表型和基因组的差异。细胞聚集，这是主要是 III 分支菌株的表型，已与某些感染模型中的毒力降低有关。因此，聚集表型与（皮肤）定植而不是全身感染相关。然而，比较具有不同分支亲缘关系的菌株，以推断不同形态对毒力的影响。这使得难以区分形态依赖性原因与分支特异性甚至菌株特异性遗传因素。在这里，我们确定了两种不同类型的聚集：一种是由抗真菌治疗引起的，是细胞分离缺陷的结果；另一种是由生长条件控制的，仅发生在具有聚集能力的菌株中。后一种聚集类型依赖于 ALS 家族黏附素，该黏附素在聚集性耳念珠菌菌株的聚集过程中差异表达。最后，我们证明巨噬细胞不能清除聚集物，这表明聚集物在全身感染过程中可能仍然有益，并可能促进其在宿主中的长期存活。
