Transposition of the Zorro2 Retrotransposon Is Activated by Miconazole in <i>Candida albicans</i>

Abstract

Zorro2 is a member of a non-long terminal repeat (LTR) retrotransposon family in Candida albicans, but as yet no clear evidence has been provided to establish either transcription or transposition activity for Zorro2. In this study, the relative expression changes of two open reading frames in Zorro2, ORF19.7274 and ORF19.7275, were examined in response to miconazole (MCZ), and were found to be increased by this treatment. As well, the copy number and the transcripts of Zorro2 in MCZ-induced resistant daughter strains were increased compared to the parental strain, indicating that transposition of Zorro2 occurred during long-term MCZ treatment. Intriguingly, the transcription activity of Zorro2 retrotransposons was significantly inhibited when the cells were treated with MCZ together with antioxidant N-acetyl-L-cysteine (NAC). As both the level of intracellular reactive oxygen species (ROS) and the expression of genes involving DNA repair activated by MCZ were reduced when combined with the treatment of NAC, we propose that the damage caused by accumulation of ROS under MCZ stress is a major reason for the transcription and transposition activation of the Zorro2 retrotransposon.

Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species‑mediated endoplasmic reticulum stress

“…ROS also act as second-messenger signaling molecules, regulating multiple cell functions, including autophagy and apoptosis (42)(43)(44). The induction of intracellular oxidative stress by miconazole has been demonstrated in rat neonatal cardiomyocytes and bladder cancer cells, as well as in Candida albicans and other fungi (18,25,(45)(46)(47)(48). The present study revealed that the NAC-mediated scavenging of miconazole-induced ROS decreased the levels of LC3-II and molecular markers of ER stress.…”

A biological and genomic comparison of a drug-resistant and a drug-susceptible strain of Candida auris isolated from Beijing, China

“…Some Zorro3 insertions are close to antifungal resistance-associated genes (Dataset S2), which may affect the expression of these genes and thus regulate antifungal susceptibility. Interestingly, the transposition of the Zorro2 retrotransposon is activated by miconazole, suggesting that these retrotransposons could be associated with antifungal resistance [37]. In C. albicans, the Zorro3 element FGR14 also regulates filamentous growth [38].…”

Candida Survival Strategies

“…These mobile elements are affected by population density and ecological aspects, e.g., stress (Arkhipova, 2005;Johnson, 2007). For example, the non-LTR retro-transposon Zorro2 is activated by miconazole treatment (Zhu et al, 2014). Activation of these transposons leads to additional copies in the C. albicans genome.…”

“…Activation of these transposons leads to additional copies in the C. albicans genome. Although the exact role of these additional copies remains to be elucidated, Zhu et al hypothesized that these retro-transposons can patch together broken chromosome ends and provide dispersed regions of homology that facilitate chromosomal rearrangements (Dunham et al, 2002;Umezu, Hiraoka, Mori, & Maki, 2002;Zhu et al, 2014). This promotes the repair of ROS-induced DNA damage and chromosomal loss, which are consequences of miconazole treatment (Zhu et al, 2014).…”