Candida starves the macrophage of sugar

A macrophage engulfs a fungus in order to destroy it. A paper in Nature Communications describes the reverse: the fungus leaves the macrophage, and its escape route rests on something as basic as competition for glucose.

The authors showed that Candida albicans and Candida auris induce glucose starvation in the macrophage, and that this activates NINJ1 — the executioner of membrane rupture during cell death. In glucose-starved macrophages NINJ1 ruptures the membrane independently of known cell death programmes. Among the host cell death factors tested, NINJ1 proved the dominant effector of fungal-induced macrophage damage.

The amino acid result was unexpected. Supplying alanine rescued starved macrophages better than supplying glucose, and it did so by inhibiting NINJ1 oligomerisation — by blocking the mechanism rather than restoring the fuel. The authors also showed that C. albicans infection disrupts amino acid metabolism in mice and lowers serum alanine.

The final link closes the story. NINJ1-mediated membrane rupture enables C. albicans to leave the macrophage, together with the toxin candidalysin. The escape is therefore not an incidental by-product of an immune cell's death but a route the fungus uses.

Two things are worth noting for a reader outside the laboratory. First, Candida auris is one of the pathogens on the WHO priority list, so the mechanism concerns a species of real hospital significance. Second, this remains basic research: it describes a mechanism and identifies a possible target, but the road from inhibiting protein oligomerisation in culture to a medicine is a long one.

The shift of emphasis here is interesting. Classical thinking about infection focuses on how a pathogen destroys a cell: by toxin, by enzyme, mechanically. In this picture the fungus destroys nothing directly — it is enough that it takes the macrophage's substrate, and the host's own protein does the rest. The damage is a consequence of the cell's defensive reaction rather than of the fungus's action.

The alanine result deserves separate attention, because it says something about metabolic dependencies. An amino acid that rescues a cell better than the missing sugar is not acting as fuel but as a regulator. It is a reminder that an immune cell's metabolism and its functions are not two separate layers but one — and that a lowered serum amino acid can be both a consequence of infection and a factor in it.

No dietary conclusions follow. Supplying alanine in cell culture and a patient eating an amino acid are two different situations, and the authors tested no intervention in humans.

Evidence status — 29 August 2026

The article was published on 10 June 2026, with the version of record posted on 27 July. In macrophage experiments, Candida albicans and C. auris caused glucose starvation that triggered NINJ1-dependent membrane rupture. For C. albicans, the work also showed that NINJ1 and candidalysin help the fungus exit the cell; in mice, infection altered amino-acid metabolism and lowered serum alanine. Alanine was a mechanistic tool that rescued cells in experiments, not a recommendation for supplementation. The result explains one stage of pathogen escape, but it does not determine treatment or the course of infection in a human patient.