Antimicrobial resistance frequently carries a fitness cost to a pathogen, measured as a reduction in growth rate compared to the sensitive wild-type, in the absence of antibiotics. Existing empirical evidence points to the following relationship between cost of resistance and virulence. If a resistant pathogen suffers a fitness cost in terms of reduced growth rate it commonly has lower virulence compared to the sensitive wild-type. If this cost is absent so is the reduction in virulence. Here we show, using experimental evolution of drug resistance in the fungal human pathogen Candida glabrata, that reduced growth rate of resistant strains need not result in reduced virulence. Phenotypically heterogeneous populations were evolved in parallel containing highly resistant sub-population small colony variants (SCVs) alongside sensitive sub-populations. Despite their low growth rate in the absence of an antifungal drug, the SCVs did not suffer a marked alteration in virulence compared with the wild-type ancestral strain, or their co-isolated sensitive strains. This contrasts with classical theory that assumes growth rate to positively correlate with virulence. Our work thus highlights the complexity of the relationship between resistance, basic life-history traits and virulence.

中文翻译：

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人类真菌病原体光滑念珠菌表型多样的耐药性和毒性小菌落的进化

在没有抗生素的情况下，抗微生物药物耐药性通常会给病原体带来健康成本，衡量标准是与敏感的野生型相比生长速度的降低。现有的经验证据表明抗性成本与毒力之间存在以下关系。如果抗性病原体因生长速度降低而遭受健康成本，与敏感的野生型相比，它通常具有较低的毒力。如果没有这个成本，那么毒力的降低也是如此。在这里，我们显示，使用真菌人类病原体光滑念珠菌中耐药性的实验进化，耐药菌株的生长速度降低不一定会导致毒力降低。表型异质种群同时进化，包含高抗性亚种群小菌落变体 (SCV) 以及敏感亚种群。尽管在没有抗真菌药物的情况下它们的增长率很低，但与野生型祖先菌株或其共同分离的敏感菌株相比，SCV 的毒力并未发生显着变化。这与假设增长率与毒力呈正相关的经典理论形成对比。因此，我们的工作突出了耐药性、基本生活史特征和毒力之间关系的复杂性。