Título:	Population heterogeneity in Cryptococcus neoformans : impact on pathogenesis
Autor(es):	Agrawal, Ruchi Castro, Raffael Júnio Araújo de Sturny-Leclère, Aude Alanio, Alexandre
ORCID:	https://orcid.org/0000-0002-5207-8892 https://orcid.org/0000-0002-0232-9390 https://orcid.org/0000-0001-9726-3082
Afiliação do autor:	Institut Pasteur, Université Paris Cité, National Reference Center for Invasive Mycoses and Antifungals, Translational Mycology Group, Mycology Department Institut Pasteur, Université Paris Cité, National Reference Center for Invasive Mycoses and Antifungals, Translational Mycology Group, Mycology Department University of Brasilia, Institute of Biological Sciences, Department of Cell Biology, Laboratory of Applied Immunology Institut Pasteur, Université Paris Cité, National Reference Center for Invasive Mycoses and Antifungals, Translational Mycology Group, Mycology Department Institut Pasteur, Université Paris Cité, National Reference Center for Invasive Mycoses and Antifungals, Translational Mycology Group, Mycology Department Hôpital Saint-Louis AP-HP, Mycology-parasitology Laboratory
Assunto:	Heterogeneidade Cryptococcus neoformans Patogênese
Data de publicação:	11-nov-2024
Editora:	PLOS
Referência:	AGRAWAL, Ruchi; CASTRO, Raffael Júnio Araújo de; STURNY-LECLÈRE, Aude; ALANIO, Alexandre. Population heterogeneity in Cryptococcus neoformans: impact on pathogenesis. PLOS Pathogens, California, v. 20, n. 7, e1012332, 2024. DOI: https://doi.org/10.1371/journal.ppat.1012332. Disponível em: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012332. Acesso em: 27 jan. 2026.
Abstract:	Cryptococcus neoformans was first isolated from a patient in 1894 [1] and 130 years later, it remains a prevalent global threat, especially for people living with human immunodeficiency virus (HIV) [2]. Human–Cryptococcus interaction begins in childhood, after inhalation of basidiospores which are widespread in the environment. Typically, this interaction advances in one of the 4 major possible ways: (I) latent/dormant (asymptomatic) cryptococcosis, where C. neoformans can hide in the host for years without any clinical symptoms; (II) pulmonary cryptococcosis (cryptococcal pneumonia), which may or may not need medical intervention depending on host’s underlying conditions; (III) disseminated cryptococcosis, where C. neoformans probably disseminates from lungs to different organs such as kidneys, bones, skin, and to the central nervous system by crossing the blood–brain barrier, after reactivation from dormancy; (IV) cryptococcal relapse, where the formerly treated infection resurfaces and requires specific medical management. Population heterogeneity (also referred to as phenotypic heterogeneity) provides a functional advantage to many microbial pathogens to survive in fluctuating conditions (please refer to this excellent review [3]). It can be defined as the preexisting diversity within an isogenic population. Population heterogeneity arises due to the phenotypic differences between individual cells in an otherwise genetically identical/homogenous population. Prominent examples of phenotypic heterogeneity (well known in bacteria but not much in fungi) are biofilm, antimicrobial persistence, heteroresistance, and cellular dormancy, which is often observed as a viable but nonculturable (VBNC) phenotype. As described further in the review, population heterogeneity provides benefits to the C. neoformans population in coping with unpredictable environmental and host conditions. It contributes to the survival of C. neoformans in challenging and ever-changing conditions such as switching from the outer atmosphere to the host lungs, from extracellular to intracellular niche (e.g., inside macrophages), from lungs to brain or other tissues, from compromised immune system to exposure to antifungal drugs.
Unidade Acadêmica:	Instituto de Ciências Biológicas (IB) Departamento de Biologia Celular (IB CEL)
Programa de pós-graduação:	Programa de Pós-Graduação em Biologia Molecular
Licença:	© 2024 Agrawal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI:	https://doi.org/10.1371/journal.ppat.1012332
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