Stress Response in Candida albicans Induced by Boric Acid

Candida albicans is an opportunistic fungal pathogen found in the oral mucosa, the gut, the vaginal mucosa, and humans' skin. While C. albicans can cause superficial infections, severe invasive infections can occur in immunocompromised individuals. Understanding the survival mechanisms and pathogenesis of C. albicans is critical for novel antifungal drug discovery. Determining the relationships between different genes can create a genetic interaction map, which can identify complementary gene sets, central to C. albicans survival, as potential drug targets in combination therapy. A genetic approach using the CRISPR-Cas9-based genome editing platform will focus on genetic interaction analysis of C. albicans stress response genes. The ultimate goal is to create a stress response gene deletion library to study its pathogen survival role. This library of single and double stress response gene mutants will be screened under diverse growth conditions to assess their relative fitness. Genetic interaction analysis will help map out epistatic interactions between fungal genes involved in growth, survival, and pathogenesis and uncover putative targets for combination antifungal therapy based on negative or synthetic lethal genetic interactions.

Download Full-text

Effects of 3% Boric Acid Solution on Cutaneous Candida albicans Infection and Microecological Flora Mice

Frontiers in Microbiology ◽

10.3389/fmicb.2021.709880 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qing Liu ◽

Zhao Liu ◽

Changlin Zhang ◽

Yanyan Xu ◽

Xiaojing Li ◽

...

Keyword(s):

Candida Albicans ◽

Acid Solution ◽

Boric Acid ◽

Clinical Manifestations ◽

Effective Rate ◽

16S Rrna Genes ◽

Rrna Genes ◽

Boric Acid Solution ◽

Cutaneous Infections ◽

Group B

To determine the effect of 3% boric acid solution on cutaneous infections with Candida albicans (CA) in mice and its effect on skin microflora. Female mice were divided into three groups, with 18 mice in each group. Two injection sites were randomly selected, and 0.1 mL of CA mycelium suspension was injected into the epidermis and dermis of the back of mice. Group N was treated with sterile water for injection (SWFI). We observed the clinical manifestations, fungal fluorescence microscopic examination and colony count. Group B were hydropathically compressed with 3% boric acid solution for 30 min every 12 h. Group M was treated with SWFI, and group N was not treated. One week later, each group was observed with naked eyes, and skin samples were collected. The effect of boric acid on skin microflora was measured using Internal Transcribed Spacer Identification (ITS) and 16S rRNA genes. There were no significant changes in group M. In group B, the degree of skin injury was alleviated, the wounds healed markedly, and the exudate amount decreased. The effective rate of group B (83%) was significantly higher than that of group M (25%) (P < 0.05). The relative average abundance of Candida (P < 0.0001) and CA (P < 0.05) in group B was significantly lower than that in group M. Compared with group M, the microbial richness of group B changed little, but the diversity decreased. The flora structure of group B was significantly different from that of group M, but like that of group N. In group B, the abundance of Proteobacteria (P < 0.001), Enterobacteriaceae (P < 0.001), and Escherichia-Shigella (P < 0.001) was significantly greater, and the abundance of Firmicutes (P < 0.001), Staphylococcaceae (P < 0.001), and Staphylococcus (P < 0.001) were significantly lower. The 3% boric acid solution significantly reduced the symptoms of skin infection with Candida albicans. It inhibited the growth of Candida albicans and CA, reduced the diversity of skin microorganisms, increased the abundance of Proteobacteria, Enterobacteriaceae, Escherichia-Shigella, and reduced the abundance of Firmicutes, Staphylococcaceae, Staphylococcus.

Download Full-text

Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in Candida albicans

mSphere ◽

10.1128/msphere.00672-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Ohimai Unoje ◽

Mengli Yang ◽

Yang Lu ◽

Chang Su ◽

Haoping Liu

Keyword(s):

Candida Albicans ◽

Stress Response ◽

Map Kinase ◽

Hyphal Growth ◽

Acidic Ph ◽

Transcriptional Repressors ◽

Growth Forms ◽

Content Type ◽

Hyphal Development ◽

Study Results

ABSTRACT Candida albicans is an important human pathogen responsible for causing both superficial and systemic infections. Its ability to switch from the yeast form to the hyphal growth form is required for its pathogenicity. Acidic pH inhibits hyphal initiation, but the nature of the mechanism for this inhibition is not completely clear. We show that acidic pH represses hyphal initiation independently of the temperature- and farnesol-mediated Nrg1 downregulation. Using a collection of transcription factor deletion mutants, we observed that the sfl1 mutant induced hyphae in acidic pH but not in farnesol at 37°C. Furthermore, transcription of hyphal regulators BRG1 and UME6 was not induced in wild-type (WT) cells but was induced in the sfl1 mutant during hyphal induction in acidic pH. Using the same screening conditions with the collection of kinase mutants, we found that deletions of the core stress response mitogen-activated protein (MAP) kinase HOG1 and its kinase PBS2, the cell wall stress MAP kinase MKC1, and the calcium/calmodulin-dependent kinase CMK1 allowed hyphal initiation in acidic pH. Furthermore, Hog1 phosphorylation induced by high osmotic stress also retarded hyphal initiation, and the effect was abolished in the sfl1 and three kinase mutants but was enhanced in the phosphatase mutant ptp2 ptp3. We also found functional associations among Cmk1, Hog1, and Sfl1 for cation stress. Our study results suggest that robust hyphal initiation requires downregulation of both Nrg1 and Sfl1 transcriptional repressors as well as timely BRG1 expression. Acidic pH and cationic stress retard hyphal initiation via the stress-responsive kinases and Sfl1. IMPORTANCE Candida albicans is a commensal as well as a pathogen of humans. C. albicans is able to mount a cellular response to a diverse range of external stimuli in the host and switch reversibly between the yeast and hyphal growth forms. Hyphal development is a key virulence determinant. Here, we studied how C. albicans senses different environmental signals to control its growth forms. Our study results suggest that robust hyphal development requires downregulation of two transcriptional repressors, Nrg1 and Sfl1. Acidic pH or cationic stress inhibits hyphal formation via stress-responsive kinases and Sfl1.

Download Full-text