Pathogenicity of Cryptococcus neoformans VNI (ST 32) recovered from environmental and clinical isolates in Nigeria

2023

Preprint

In this review, we present several extracellular proteases, enzymes, membrane permeases, and transporters as essential accessories proteins for nutrient assimilation, conservation, and transportation as determined by nutrient repletion or depletion. As an obligate aerobic pathogen, it is crucial for invading Cryptococcus (C.) neoformans to negotiate its adaptation to human internal organs like the brain and spinal cord, where the oxygen level is low compared to peripheral organs. Besides, essential metals like copper and iron are important cofactors to functional proteins; however, these metals are not usually freely available to invading human pathogens. Again, the phagolysosome low pH with glucose paucity, internal temperature, immune response, and complex extracellular matrixes are challenging environments that must be circumvented by C. neoformans in the systemic tissues for survival, adaptation, and infection in humans. We review extensive works on several extracellular proteases, enzymes, membrane permeases and transporters orchestrated by different transcription factors and present these proteins as weapons needed to outwit systemic resistance to invading pathogens. Lastly, we examine the extracellular secretory vesicles of C. neoformans as “an exosomal virulence bag” that harbours urease, laccase, phosphatase, and capsular components as additional secretory weapons for tissue invasion and persistence.

Section: Introductionmentioning

confidence: 81%

Hydrolytic Enzymes, Proteases, Permeases, and Transporters as Cryptococcus neoformans Weapons in Human Infections

Folorunso¹,

2023

Preprint

“…Based on their immediate interaction, cryptococcal cells could be environmental or clinical. Both showed similar pathogenicity in animal models [27] because of the similarity in the virulence factors capsule, melanin, extracellular secretory hydrolytic enzymes (like urease, phosphatase, DNase, lipase, protease, glycosidase), and membrane-associated enzymes (like laccase, IPC synthase, chitin synthase, catalase, and superoxide dismutase) [28]. Via the nutrient sensors like cAMP/Pka, Gpr1, Gpr4, Aap, Gpp2, and Hxt1, C. neoformans reprogram gene expressions to survive inadequate nutrient bioavailability and nutrient adaptation [29].…”

Section: Introductionmentioning

confidence: 81%

Transcription Factors Control the Virulence-Associated Metabolic Enzymes and Membrane Proteins in Response to Nutrient Bioavailability in Cryptococcal Infection

Folorunso¹,

2023

Preprint

Cryptococcus neoformans is a pathogenic fungus that causes cryptococcosis, a significant secondary infection in immunocompromised individuals with immune-suppressive related symptoms from HIV infection and organ transplants. Fungaemia occurs via the respiratory route and spreads by tissue invasion into other body parts. Enzymes and membrane-associated permeases/transporters are accessory proteins deployed to enhance the survival, adaptation, and infection caused by Cryptococcus species. The nutrient bioavailability determines the functional turnover rate of these proteins in the immediate fungal environment. Low oxygen levels in the internal organs, essential micro-elements locked in the storage proteins, catabolite repression, phagolysosomal low glucose level and pH, tight junction, and extracellular matrixes are challenges to the survival of this pathogen in the host. This review identifies key hydrolytic and metabolic enzymes and permeases/transporters as essential weapons of virulence in addition to survival, tolerance, resistance, adaptation, and infection in humans. Under the regulation of different transcription factors, these proteins are released in response to nutrient sensors designed to siphon the host nutrients and induce infection in predisposed individuals. The extracellular secretory vesicles called “exosomal virulence bag” also harbour cryptococcal urease, laccase, phosphatase, and capsular components as additional secretory protein weapons for immune evasion, tissue invasion and persistence.

“…This pattern of infection re-emphasises why the immunocompromised individual is predisposed to cryptococcosis. By spore-inhalation, the C. neoformans pathogen becomes invasive (cryptococcemia) from the lungs to other parts of the body tissues and organs, particularly the CNS, brain, bones, skin, prostate, and heart [11].…”

Section: Introductionmentioning

confidence: 99%

“…Early investigation showed that environmental isolates might be less virulent in the animal model compared to the clinical isolate [14]. However, a recent study has shown that the pathogenicity of the VNI strain, whether an environmental or a clinical isolate, was the same in the animal model [11].…”

Section: Introductionmentioning

confidence: 99%

Transcription Factors and Intracellular Proteins Orchestrate Phenotypic Adaptation in Cryptococcus neoformans for Survival and Human Infections

Folorunso¹,

2023

Preprint

Transcription factors are diverse intracellular proteins facilitating cellular responses to inducing factors via gene expression. Regulatory signalling cascades from the membrane proteins (sensors) to transcription factors (effectors) are paramount to accurate phenotypic display against external factors. This review examines several transcription factors germane to Cryptococcus (C.) neoformans adaptation and survival for human infection. These opportunistic pathogenic single-cell yeasts (fungi) possess several gene duplications and peculiar membrane proteins due to adaptive phenotypes and morphological plasticity. Consequently, hundreds of responsible pleiotropic genes have been studied to understand how these genes are induced, regulated, and coordinated. However, these findings are sparsely converged and interlinked, making it cumbersome to relate one gene to the other or group them by their functions. We reviewed several wide-ranging transcriptional analysis works associated with C. neoformans into comparable phenotypic traits that necessitate adaptation, survival, and human infection. We present a robust work that addresses several transcription factors and their inducing factors. Lastly, we converge, link, and group several of these factors according to their multifunctional expression pattern. We also provide adequate information on certain genes critical to this fungus, which could be explored pharmaceutically in drug targeting for more effective antifungal management.