Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain

Abstract

Cryptococcus neoformans is an opportunistic pathogenic yeast that causes serious infections, most commonly of the central nervous system (CNS). C. neoformans is mainly found in the environment and acquired by inhalation. It could be metaphorically imagined that cryptococcal disease is a “journey” for the microorganism that starts in the environment, where this yeast loads its suitcase with virulence traits. C. neoformans first encounters the infected mammalian host in the lungs, a site in which it must choose the right elements from its “virulence suitcase” to survive the pulmonary immune response. However, the lung is often only the first stop in this journey, and in some individuals the fungal trip continues to the brain. To enter the brain, C. neoformans must “open” the main barrier that protects this organ, the blood brain barrier (BBB). Once in the brain, C. neoformans expresses a distinct set of protective attributes that confers a strong neurotropism and the ability to cause brain colonisation. In summary, C. neoformans is a unique fungal pathogen as shown in its ability to survive in the face of multiple stress factors and to express virulence factors that contribute to the development of disease.

Diversity, Virulence Factors, and Antifungal Susceptibility Patterns of Pathogenic and Opportunistic Yeast Species in Rock Pigeon (Columba livia) Fecal Droppings in Western Saudi Arabia

“…Wu et al (2012) reported the presence of eight different genera of yeast, such as Cryptococcus, Candida, Diversity, Virulence Factors, and Antifungal Susceptibility Patterns of Pathogenic and Opportunistic Yeast Species in Rock Pigeon (Columba livia) Fecal Droppings in Western Saudi Arabia suggest that there are around 220 000 annual cases of cryptococcal meningitis in HIV patients worldwide. Therefore, cryptococcal meningitis may be the leading cause of death among HIV patients (Cogliati 2013; Hagen et al 2015;Rajasingham et al 2017;Esher et al 2018;Magalhães Pinto et al 2019).…”

Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans

“…First, we could not track down the genes involved in neurotropism of C. neoformans, due to a lack of proper known systems. It has been hypothesised that C. neoformans has a neurotropism to the CNS to utilise neurotransmitters 13 . Therefore, some of the kinase and TF mutants may have reduced brain-STM scores because of a lack of neurotropism.…”

“…Among the infection stages, crossing the blood-brain barrier (BBB) and proliferation in the brain parenchyma are critical factors for C. neoformans to impose lethal lesions in mammalian brain tissues. C. neoformans is able to traverse the BBB, which protects the brain from pathogens because of the establishment of tight junctions between brain microvascular endothelial cells (BMECs) and the contribution of brain astrocytes 12 , through transcellular, paracellular, and/or Trojan-horse mechanisms 13,14 . Nevertheless, the complex signalling pathways regulating these known and hitherto uncharacterised factors governing the BBB crossing and brain infection of C. neoformans are not completely understood.…”

Cryptococcus neoformans-Host Interactions Determine Disease Outcomes

“…Cryptococcal virulence includes evasion of immune recognition, interference with phagocytosis, and modulation of host immune responses [56,99]. Many fungal factors have been shown to promote allergic Th2 or Treg responses.…”