Evidence map›Paper›PMID 30291809›Full record

ArticleCellular microbiology2019

Role of clathrin-mediated endocytosis in the use of heme and hemoglobin by the fungal pathogen Cryptococcus neoformans.

Gaurav Bairwa, Mélissa Caza, Linda Horianopoulos, Guanggan Hu, James Kronstad

Open access · bronzeAbstract read
In one paragraph

Article in Cellular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Heme sensing and trafficking in fungi.Fungal biology reviews · 2023
    Article
  13. Targeting ferroptosis: a novel insight against myocardial infarction and ischemia-reperfusion injuries.Apoptosis : an international journal on programmed cell death · 2023
    Review
  14. Article
  15. Article
  16. Cryptococcus spp. and Cryptococcosis: focusing on the infection in Brazil.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022
    Review
  17. Article
  18. Review
  19. Article
  20. Interacting with Hemoglobin:Journal of fungi (Basel, Switzerland) · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Gaurav BairwaMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Mélissa CazaMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Linda HorianopoulosMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Guanggan HuMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
James KronstadMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0003-4240-6976
University of British Columbia · CA

Funding

Comparative and functional genomics of C. neoformansR01AI053721 · NIAID · UNIVERSITY OF BRITISH COLUMBIA · PI KRONSTAD, JAMES W · 2003 to 2024
$5.4M
NIAID NIH HHS R01 AI053721
6 · The paper itself

Abstract

Heme is a major source of iron for pathogens of humans, and its use is critical in determining the outcome of infection and disease. Cryptococcus neoformans is an encapsulated fungal pathogen that causes life-threatening infections in immunocompromised individuals. C. neoformans effectively uses heme as an iron source, but the underlying mechanisms are poorly defined. Non-iron metalloporphyrins (MPPs) are toxic analogues of heme and are thought to enter microbial cells via endogenous heme acquisition systems. We therefore carried out a mutant screen for susceptibility against manganese MPP (MnMPP) to identify new components for heme uptake in C. neoformans. We identified several genes involved in signalling, DNA repair, sugar metabolism, and trafficking that play important roles in susceptibility to MnMPP and in the use of heme as an iron source. We focused on investigating the role of clathrin-mediated endocytosis (CME) and found that several components of CME including Chc1, Las17, Rvs161, and Rvs167 are required for growth on heme and hemoglobin and for endocytosis and intracellular trafficking of these molecules. We show that the hemoglobin uptake process in C. neoformans involves clathrin heavy chain, Chc1, which appears to colocalise with hemoglobin-containing vesicles and to potentially assist in proper delivery of hemoglobin to the vacuole. Additionally, C. neoformans strains lacking Chc1, Las17, Rvs161, or Rvs167 were defective in the elaboration of several key virulence factors, and a las17 mutant was avirulent in a mouse model of cryptococcosis. Overall, this study unveils crucial functions of CME in the use of heme iron by C. neoformans and reveals a role for CME in fungal pathogenesis.

Indexed as

EndocytosisAnimalsClathrinClathrin-Coated VesiclesCryptococcus neoformansGenetic TestingHemeHemoglobinsIronManganeseMiceVirulence FactorsClathrinHemeHemoglobinsIronManganeseVirulence FactorsCHC1clathrinCryptococcusendocytosishemehemoglobiniron

Identifiers

PMID30291809
PMCPMC6379112
OpenAlexW2950037712

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.