Abstract
An ORF named CPAR2-208980 on contig 005809 was identified by screening a Candida parapsilosis genome data base. Its 67% identity with the acid trehalase sequence from C. albicans (ATC1) led us to designate it CpATC1. Homozygous mutants that lack acid trehalase activity were constructed by gene disruption at the two CpATC1 chromosomal alleles. Phenotypic characterization showed that atc1Δ null cells were unable to grow on exogenous trehalose as carbon source, and also displayed higher resistance to environmental challenges, such as saline exposure (1.2 M NaCl), heat shock (42°C) and both mild and severe oxidative stress (5 and 50 mM H2O2). Significant amounts of intracellular trehalose were specifically stored in response to the thermal upshift in both wild type and mutant strains. Analysis of their antioxidant activities revealed that catalase was only triggered in response to heat shock in atc1Δ cells, whereas glutathione reductase was activated upon mild oxidative stress in wild type and reintegrant strains, and in response to the whole set of stress treatments in the homozygous mutant. Furthermore, yeast cells with double CpATC1 deletion were significantly attenuated in non-mammalian infection models, suggesting that CpATC1 is required for the pathobiology of the fungus. Our results demonstrate the involvement of CpAtc1 protein in the physiological hydrolysis of external trehalose in C. parapsilosis, where it also plays a major role in stress resistance and virulence.
Highlights
Several yeast species are included among the most dangerous microorganisms that cause opportunistic infections in humans and mammals
An ORF named CPAR2-208980 was found on contig 005809, which presented 67% nucleotide sequence homology with ATC1 from C. albicans [13], and 62% homology at protein level
Similar homology was found after comparison of the predicted amino acid sequence with the sequences found in protein data bases using the BLAST search algorithm [33] for C. albicans Atc1 [13] and S. cerevisiae Ath1 [34]
Summary
Several yeast species are included among the most dangerous microorganisms that cause opportunistic infections in humans and mammals. Often considered less virulent than C. albicans, C. parapsilosis is the Candida species with the largest increase in clinical incidence in recent decades [4,5]. It causes multifaceted pathologies in immunocompromised and normal hosts, especially low birth weight neonates. The dramatic extension of opportunistic mycosis, especially among the debilitated and ageing population, and the worrying isolation of fungal strains resistant to conventional antibiotics points to the need for more efficient and selective antifungal compounds In this context, the non-reducing disaccharide trehalose has been studied as a potentially interesting antifungal target [7,8,9]. The CpATC1-deficient mutants were more resistant to in vitro stress exposure, but more sensitive to immune system clearance after in vivo infection than its parental counterpart, suggesting a major role for the CpATC1 gene in C. parapsilosis virulence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
