Virulence of the fungal pathogen Candida albicans requires the five isoforms of protein mannosyltransferases

Mahmoud Rouabhia1, Martin Schaller, Cristina Corbucci

  • 1Institut for Mikrobiologie, Universitätsstr. 1/26.12, 40225 Düsseldorf, Germany.

Insights

All protein mannosyltransferase (Pmt) gene mutants in Candida albicans showed reduced virulence in mouse and human tissue models. Individual Pmt isoforms have varied importance in different host environments, suggesting potential antifungal targets.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Candida albicans utilizes protein mannosyltransferases (Pmt) to initiate O-mannosylation of secretory proteins.
  • The PMT gene family comprises five isoforms: Pmt1p, Pmt2p, Pmt4p, Pmt5p, and Pmt6p.

Purpose of the Study:

  • To investigate the contribution of individual Pmt isoforms to Candida albicans virulence.
  • To compare the virulence of pmt mutants in distinct in vitro and in vivo models of candidiasis.

Main Methods:

  • Utilized reconstituted human epithelium (RHE) and engineered human oral mucosa (EHOM) as 3D models for localized candidiasis.
  • Employed a mouse model of hematogenously disseminated candidiasis (HDC).
  • Assessed virulence characteristics of various pmt mutants.

Main Results:

  • All pmt mutants exhibited attenuated virulence in the HDC model and at least one localized candidiasis model.
  • The pmt5 mutant showed reduced virulence in EHOM and HDC models but not RHE.
  • The pmt4 and pmt6 mutants were less virulent in RHE and HDC models but not EHOM.

Conclusions:

  • All Pmt isoforms contribute to Candida albicans virulence.
  • The significance of individual Pmt isoforms varies across different host niches.
  • Pmt proteins represent potential targets for novel antifungal agents.

Related Concept Videos

Candidiasis01:20

Candidiasis

Candidiasis is a fungal infection caused by opportunistic species of Candida. It can affect various anatomical sites, including the skin, oral cavity, nails, and genitourinary tract. Among its forms, vaginal candidiasis is the most common type of mucosal infection. It typically results from the overgrowth of Candida albicans in the vaginal mucosa. Under normal conditions, C. albicans exists as a commensal organism within the vaginal microbiota, regulated by the dominance of lactobacilli, which...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
Fungal Group Zygomycota01:29

Fungal Group Zygomycota

Zygomycota, previously classified as a distinct fungal group, are primarily terrestrial, saprophytic molds that play a crucial role as decomposers. Recent phylogenetic studies have revealed that these fungi are now divided into two major clades — Mucoromycota, which includes many symbiotic species, and Zoopagomycota, which primarily consists of parasitic and pathogenic fungi. These groups exhibit distinct ecological roles and reproductive strategies while sharing key structural and...
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
Fungal Phylum Ascomycota01:28

Fungal Phylum Ascomycota

Phylum Ascomycota, a major division within the subkingdom Dikarya, comprises a diverse range of fungal species, including both unicellular yeasts and filamentous molds such as Aspergillus and Penicillium. These fungi thrive in a variety of habitats, from aquatic ecosystems to terrestrial environments, playing crucial ecological and economic roles.Morphology and ReproductionThe defining characteristic of Ascomycetes, commonly referred to as sac fungi, is the ascus—a sac-like structure that...