Infection with<unk>  is termed<unk> is. Most infections with<unk>  occur in the lungs. However, fungal meningitis and encephalitis, especially as a secondary infection for AIDS patients, are often caused by<unk> , making it a particularly dangerous fungus. Infections with this fungus are rare in people with fully functioning immune systems, hence<unk>  is often referred to as an opportunistic pathogen. It is a facultative intracellular pathogen that can utilize host phagocytes to spread within the body.<unk>  was the first intracellular pathogen for which the non-lytic escape process termed vomocytosis was observed. It has been speculated that this ability to manipulate host cells results from environmental selective pressure by amoebae, a hypothesis first proposed by Arturo Casadevall under the term "accidental virulence". In human infection,<unk>  is spread by inhalation of aerosolized basidiospores, and can disseminate to the central nervous system, where it can cause meningoencephalitis. In the lungs,<unk>  cells are phagocytosed by alveolar macrophages. Macrophages produce oxidative and nitrosative agents, creating a hostile environment, to kill invading pathogens. However, some<unk>  cells can survive intracellularly in macrophages. Intracellular survival appears to be the basis for latency, disseminated disease, and resistance to eradication by antifungal agents. One mechanism by which<unk>  survives the hostile intracellular environment of the macrophage involves upregulation of expression of genes involved in responses to oxidative stress. Traversal of the blood–brain barrier by<unk>  plays a key role in meningitis pathogenesis. However, precise mechanisms by which it passes the blood-brain barrier are still unknown; one recent study in rats suggested an important role of secreted serine proteases. The metalloprotease Mpr1 has been demonstrated to be critical in blood-brain barrier penetration. Meiosis (sexual reproduction), another possible survival factor for intracellular<unk>  The vast majority of environmental and clinical isolates of<unk>  are mating type alpha. Filaments of mating type alpha have haploid nuclei ordinarily, but these can undergo a process of diploidization (perhaps by endoduplication or stimulated nuclear fusion) to form diploid cells termed blastospores. The diploid nuclei of blastospores are able to undergo meiosis, including recombination, to form haploid basidiospores that can then be dispersed. This process is referred to as monokaryotic fruiting. Required for this process is a gene designated dmc1, a conserved homologue of genes recA in bacteria, and rad51 in eukaryotes (see articles recA and rad51). Dmc1 mediates homologous chromosome pairing during meiosis and repair of double-strand breaks in DNA. One benefit of meiosis in<unk>  could be to promote DNA repair in the DNA-damaging environment caused by the oxidative and nitrosative agents produced in macrophages. Thus,<unk>  can undergo a meiotic process, monokaryotic fruiting, that may promote recombinational repair in the oxidative, DNA-damaging environment of the host macrophage, and this may contribute to its virulence.
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