A chemically-induced attenuated strain ofCandida albicansgenerates robust protective immune response and prevents systemic candidiasis development

Abstract

AbstractDespite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine has a priority. Here, we could for the first time successfully attenuate the virulence ofCandida albicansby treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live-whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation ofC. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell-wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected inCa-vsCAET-challenged mice. While hyper-inflammation caused the killing ofCa-challenged mice, a critical balance of pro- and anti-inflammatory cytokines are the likely reasons for the protective immunity in CAET-infected mice.