Pathogenesis and virulence of Candida albicans

ABSTRACT

Candida albicans is a commensal yeast fungus of the human oral, gastrointestinal, and genital mucosal surfaces, and skin. Antibiotic-induced dysbiosis, iatrogenic immunosuppression, and/or medical interventions that impair the integrity of the mucocutaneous barrier and/or perturb protective host defense mechanisms enable C. albicans to become an opportunistic pathogen and cause debilitating mucocutaneous disease and/or life-threatening systemic infections. In this review, we synthesize our current knowledge of the tissue-specific determinants of C. albicans pathogenicity and host immune defense mechanisms.

KEYWORDS:

• Candida albicans
• candidiasis
• pathogenesis
• virulence
• immunity
• host-pathogen interactions

Abbreviations

Vulvovaginal candidiasis (VVC), Oropharyngeal candidiasis (OPC), Esophageal candidiasis (EPC), Central nervous system (CNS), Antimicrobial peptides (AMPs), Platelet-derived growth factor BB (PDGF BB), Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), Epidermal growth factor receptor (EGFR), Secreted aspartic proteinases (Saps), N-acetylglucosamine (GlcNAc), Superoxide dismutases (Sods), Reactive oxygen species (ROS), Heat shock proteins (Hsps), Pathogen-associated molecular patterns (PAMPs), Pattern recognition receptors (PRR), MAPK (mitogen-activated protein kinase), CEK1 (Choline/ethanolamine kinase 1), C-type lectin receptors (CLRs), Spleen tyrosine kinase (SYK), Caspase recruitment domain-containing protein 9 (CARD9), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NF-κB-inducing kinase (NIK), Neutrophil extracellular traps (NETs), Primary immunodeficiency disorder (PID), Recurrent VVC (RVVC), Toll-like receptors (TLRs), Intensive care unit (ICU), NOD-like receptors (NLRs), Nicotinamide adenine dinucleotide phosphate (NADPH), Chronic mucocutaneous candidiasis (CMC), monoclonal antibodies (mAbs), Inflammatory bowel disease (IBD), type 3 innate lymphoid cells (ILC3), Dendritic cells (DCs), natural Th17 (nTh17), Tissue-resident memory T cells (T_RM), Granulocyte colony-stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GM-CSF), Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), Autoimmune polyglandular syndrome type 1 (APS-1), Autoimmune regulator (AIRE), Interferon gamma (IFN-γ), IL-1 receptor antagonist (IL-1Ra), Phosphoglycerate mutase (Gpm1), Calcitonin gene-related peptide (CGRP), T cell receptor (TCR), Complement receptor 3 (CR3), PKCδ (protein kinase delta), NFAT (Nuclear factor of activated T cells), Protein arginine deiminase 4 (PAD4), Myeloperoxidase enzyme (MPO), Jagunal homolog 1 (JAGN1), Protein kinase C (PKC), Phosphoinositide-3-kinase (PI3K), Suppressor of TCR signaling (Sts), Dendritic cell natural killer lectin group receptor-1 (DNGR-1), Renal tubular epithelial cells (RTECs), Glutathione reductase (Gsr), Glycogen synthase kinase 3 beta (GSK3β), 5-flucytosine (5-FC), Amphotericin B (AMB).

Acknowledgments

We apologize to those colleagues whose papers could not be cited due to space limitations.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

No data sets were analyzed in this manuscript, and data availability is not applicable.

Notes

1. In all subheadings, the PDF proof does not have a line to separate the previous from the next subsection. please add a line of separation to make it easy for the reader to discern when a segment changes-throughout the paper

2. In Table 2, in the PDF Proof (not in here), there are words that belong in the above sentence that are shown in the sentence below. Eg in IL-12p40 deficiency NTM and infections are separately by a line and they shouldn't. Same for LAD-1 where gram-negative and bacteria, periodontitis are separately by a line. Also there is an indent in the genes listed for SCID in the PDF and in the genes listed for CGD. they should all be listed without an indent.

3. as mentioned above, subsegments are separated well here but not on the PDF proof.

Additional information

Funding

This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH; Division of Intramural Research, National Institute of Allergy and Infectious Diseases [ZIA AI001175].