Global Transcriptomic Analysis of the Candida albicans Response to Treatment with a Novel Inhibitor of Filamentation

Jesus A. Romo, Hao Zhang, Hong Cai, David Kadosh, Julia R. Koehler, Stephen P. Saville, Yufeng Wang, Jose L. Lopez-Ribot

Research output: Contribution to journalArticle

Abstract

The opportunistic pathogenic fungus Candida albicans can cause devastating infections in immunocompromised patients. Its ability to undergo a morphogenetic transition from yeast to filamentous forms allows it to penetrate tissues and damage tissues, and the expression of genes associated with a number of pathogenetic mechanisms is also coordinately regulated with the yeast-to-hypha conversion. Therefore, it is widely considered that filamentation represents one of the main virulence factors of C. albicans We have previously identified N-[3-(allyloxy)-phenyl]-4-methoxybenzamide (compound 9029936) as the lead compound in a series of small-molecule inhibitors of C. albicans filamentation and characterized its activity both in vitro and in vivo This compound appears to be a promising candidate for the development of alternative antivirulence strategies for the treatment of C. albicans infections. In this study, we performed RNA sequencing analysis of samples obtained from C. albicans cells grown under filament-inducing conditions in the presence or absence of this compound. Overall, treatment with compound 9029936 resulted in 618 upregulated and 702 downregulated genes. Not surprisingly, some of the most downregulated genes included well-characterized genes associated with filamentation and virulence such as SAP5, ECE1 (candidalysin), and ALS3, as well as genes that impact metal chelation and utilization. Gene ontology analysis revealed an overrepresentation of cell adhesion, iron transport, filamentation, biofilm formation, and pathogenesis processes among the genes downregulated during treatment with this leading compound. Interestingly, the top upregulated genes suggested an enhancement of vesicular transport pathways, particularly those involving SNARE interactions.IMPORTANCE These results from whole-genome transcriptional profiling provide further insights into the biological activity and mode of action of a small-molecule inhibitor of C. albicans filamentation. This information will assist in the development of novel antivirulence strategies against C. albicans infections.

Original languageEnglish (US)
JournalmSphere
Volume4
Issue number5
DOIs
StatePublished - Sep 11 2019

Fingerprint

Candida albicans
Genes
Down-Regulation
Yeasts
Infection
RNA Sequence Analysis
SNARE Proteins
Gene Ontology
Hyphae
Immunocompromised Host
Virulence Factors
Biofilms
Cell Adhesion
Virulence
Fungi
Iron
Metals
Genome
Gene Expression

Keywords

  • antivirulence
  • Candida albicans
  • candidiasis
  • filamentation

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Global Transcriptomic Analysis of the Candida albicans Response to Treatment with a Novel Inhibitor of Filamentation. / Romo, Jesus A.; Zhang, Hao; Cai, Hong; Kadosh, David; Koehler, Julia R.; Saville, Stephen P.; Wang, Yufeng; Lopez-Ribot, Jose L.

In: mSphere, Vol. 4, No. 5, 11.09.2019.

Research output: Contribution to journalArticle

Romo, Jesus A. ; Zhang, Hao ; Cai, Hong ; Kadosh, David ; Koehler, Julia R. ; Saville, Stephen P. ; Wang, Yufeng ; Lopez-Ribot, Jose L. / Global Transcriptomic Analysis of the Candida albicans Response to Treatment with a Novel Inhibitor of Filamentation. In: mSphere. 2019 ; Vol. 4, No. 5.
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