Heteroresistance to fluconazole may predict difficulty in clearing Candida glabrata infections

What is it about?

Heteroresistance is the appearance of a small subpopulation of cells that are able to grow at drug concentrations that inhibit growth of the majority of cell population. Here we show that C. glabrata isolates have a range of levels of heteroresistance to fluconazole, the most widely used antifungal. Highly heteroresistant isolates have higher levels of efflux activity, suggesting that they reduce intracellular drug concentrations. In a study of systemic candidiasis using a mouse model, a strain with high heteroresistance was not cleared as effectively from kidney tissue as a strain with low levels of heteroresistance.

Featured Image

Why is it important?

Heteroresistant to fluconazole is important because it may explain the failure to treat individual infections that appear to be drug-susceptible, when tested in conventional assays that measure minimal inhibitory concentration. Furthermore, subpopulations of heteroresistant cells that grow despite the inhibitory drug concentration, may drive the subsequent appearance of resistance.

Perspectives