A small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase

Abstract

The fungus Candida albicans is an opportunistic pathogen that can exploit imbalances in microbiome composition to invade its human host, causing pathologies ranging from vaginal candidiasis to fungal sepsis. Bacteria of the genus Lactobacillus are colonizers of human mucosa and can produce compounds with bioactivity against C. albicans. Here, we show that some Lactobacillus species produce a small molecule under laboratory conditions that blocks the C. albicans yeast-to-filament transition, an important virulence trait. It remains unexplored whether the compound is produced in the context of the human host. Bioassay-guided fractionation of Lactobacillus-conditioned medium linked this activity to 1-acetyl-β-carboline (1-ABC). We use genetic approaches to show that filamentation inhibition by 1-ABC requires Yak1, a DYRK1-family kinase. Additional biochemical characterization of structurally related 1-ethoxycarbonyl-β-carboline confirms that it inhibits Yak1 and blocks C. albicans biofilm formation. Thus, our findings reveal Lactobacillus-produced 1-ABC can prevent the yeast-to-filament transition in C. albicans through inhibition of Yak1.

Microbial metabolites: cause or consequence in gastrointestinal disease?

“…Hemolysin BL inhibited tumor growth in mice, providing a possible molecular explanation for the susceptibility to colorectal cancer and a potential therapeutic lead that can be further developed ( 125 ). Recently, 1-ethoxycarbonyl-β-carboline produced by Lactobacillus species was identified by bioactivity-guided fractionation as a bioactive compound against the opportunistic pathogen C. albicans ( 148 ). This molecule hinders C. albicans filamentation.…”

Intestinal Infection of Candida albicans: Preventing the Formation of Biofilm by C. albicans and Protecting the Intestinal Epithelial Barrier

“…Additional biochemical characterization of structurally related 1-ethoxycarbonyl-β-carboline confirms that it inhibits Yak1 and blocks C. albicans biofilm formation. Thus, our findings reveal Lactobacillus-produced 1-ABC can prevent the yeastto-filament transition in C. albicans through inhibition of Yak1 in vitro and vivo (MacAlpine et al, 2021). Graham et al (2017) reported that recognition of the E. faecalis bacteriocin, EntV [generated from the entV (ef1097) locus], is essential and adequate for decreasing C. albicans virulence and biofilm generation by inhibiting hyphal generation in vitro and vivo research (Graham et al, 2017).…”

The Entomopathogenic Fungus Beauveria bassiana Shows Its Toxic Side within Insects: Expression of Genes Encoding Secondary Metabolites during Pathogenesis

“…Thus, this should be the next step towards linking this process with virulence. Although there is abundant information about secondary metabolites and other small molecules in dimorphic transitions and virulence in human pathogenic fungi [ 46 , 47 , 48 ], it is still an underexplored topic in entomopathogenic fungi. A detailed study by Boucias et al [ 42 ] detected an in vivo quorum sensing system involved in M. rileyi transition from yeast-like cells to mycelia, a process that begins with the host tissue invasion stage and then culminates with insect death.…”