Dataset Information

Environmental Factors That Contribute to the Maintenance of Cryptococcus neoformans Pathogenesis.

ABSTRACT: The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host-pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission. The non-transmittable fungal pathogens, such as Cryptococcus, probably return into the environment upon decomposition of the infected host. This review analyses whether re-entry of the pathogen into the environment causes restoration of its non-pathogenic state or whether environmental factors and parameters assist them in maintaining pathogenesis. Cryptococcus (C.) neoformans is therefore used as a model organism to evaluate the impact of environmental stress factors that aid the survival and pathogenesis of C. neoformans intracellularly and extracellularly.

SUBMITTER: Maliehe M

PROVIDER: S-EPMC7074686 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Environmental Factors That Contribute to the Maintenance of <i>Cryptococcus neoformans</i> Pathogenesis.

Maliehe Maphori M Ntoi Mathope A MA Lahiri Shayanki S Folorunso Olufemi S OS Ogundeji Adepemi O AO Pohl Carolina H CH Sebolai Olihile M OM

Microorganisms 20200128 2

The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host-pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission. The non-transmittable fungal pathogens, such as <i>Cryptococcus,</i> probably return into the environment upon deco ...[more]

PMID: 32012843

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Project description:Prenyltransferase enzymes promote the membrane localization of their target proteins by directing the attachment of a hydrophobic lipid group at a conserved C-terminal CAAX motif. Subsequently, the prenylated protein is further modified by postprenylation processing enzymes that cleave the terminal 3 amino acids and carboxymethylate the prenylated cysteine residue. Many prenylated proteins, including Ras1 and Ras-like proteins, require this multistep membrane localization process in order to function properly. In the human fungal pathogen Cryptococcus neoformans, previous studies have demonstrated that two distinct forms of protein prenylation, farnesylation and geranylgeranylation, are both required for cellular adaptation to stress, as well as full virulence in animal infection models. Here, we establish that the C. neoformans RAM1 gene encoding the farnesyltransferase β-subunit, though not strictly essential for growth under permissive in vitro conditions, is absolutely required for cryptococcal pathogenesis. We also identify and characterize postprenylation protease and carboxyl methyltransferase enzymes in C. neoformans. In contrast to the prenyltransferases, deletion of the genes encoding the Rce1 protease and Ste14 carboxyl methyltransferase results in subtle defects in stress response and only partial reductions in virulence. These postprenylation modifications, as well as the prenylation events themselves, do play important roles in mating and hyphal transitions, likely due to their regulation of peptide pheromones and other proteins involved in development. IMPORTANCE Cryptococcus neoformans is an important human fungal pathogen that causes disease and death in immunocompromised individuals. The growth and morphogenesis of this fungus are controlled by conserved Ras-like GTPases, which are also important for its pathogenicity. Many of these proteins require proper subcellular localization for full function, and they are directed to cellular membranes through a posttranslational modification process known as prenylation. These studies investigate the roles of one of the prenylation enzymes, farnesyltransferase, as well as the postprenylation processing enzymes in C. neoformans. We demonstrate that the postprenylation processing steps are dispensable for the localization of certain substrate proteins. However, both protein farnesylation and the subsequent postprenylation processing steps are required for full pathogenesis of this fungus.

Dataset Information

Environmental Factors That Contribute to the Maintenance of Cryptococcus neoformans Pathogenesis.

Publications

Environmental Factors That Contribute to the Maintenance of <i>Cryptococcus neoformans</i> Pathogenesis.

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