JMM Editor's Choice: using genetics to identify new antifungal targets

Posted on October 4, 2019   by Microbiology Society

The Journal of Medical Microbiology (JMM) is a journal published by the Microbiology Society, focused on providing a comprehensive coverage of medical, dental and veterinary microbiology and infectious diseases, including bacteriology, virology, mycology and parasitology. This month, Dr Stephen Michell has selected an outstanding paper from the October issue to highlight as Editor's Choice. The paper, titled 'Sensitivity of the Candida albicans trehalose-deficient mutants tps1Δ and tps2Δ to amphotericin B and micafungin' discusses a potential new target for antifungal medication.

This article by Guirao-Abad et al., provides a genetic link to their previous observations into the fungicidal activity of amphotericin B towards Candida albicans. tps1 null strains of C. albicans, deficient in the production of trehalose through a lack of trehalose-6P synthase, exhibited a reduced oxidative response to amphotericin B – a phenotype characteristic of amphotericin B mediated antifungal activity. These findings support the need for an increased focus on trehalose as a potential target for novel therapeutics. Trehalose, a glucose disaccharide, is a previously well characterised virulence factor of several fungal and bacterial species, particularly the actinomycetes. Its emerging roles in fungal biology will be of interest to follow, especially in the development of novel antifungals.

Sensitivity of the Candida albicans trehalose-deficient mutants tps1Δ and tps2Δ to amphotericin B and micafungin

Juan Carlos Argüelles: Fungal infections have dramatically increased in the last two decades, particularly associated to the growing immunocompromised population. The available arsenal of antifungals is limited by the low selective toxicity, because the fungi are eukaryotic organisms. The search for safer and more potent antifungals should focus on targets exclusively present in pathogens and absent in hosts. Thus, the trehalose biosynthetic pathway is a promising candidate, since vertebrates lack this functional pathway. Homozygous mutants deficient in trehalose-biosynthesis of the opportunistic yeast Candida albicans showed sensitivity to the widely prescribed compounds amphotericin B and micafungin. This finding lends weight to the antifungal strategy.