Abstract

ABSTRACT Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningitis, mainly in immunocompromised individuals, such as those with HIV. Its recent detection on the International Space Station raises concerns about potential health risks in space, where immune systems may be compromised. However, its behavior in space-like conditions remains unclear. In this study, we examined the effects of simulated microgravity on C. neoformans. We found that the condition enhanced the fungus’s resistance to membrane and osmotic stress and increased key virulence factors, including capsule formation, melanin production, and urease activity. Using Caenorhabditis elegans as a host model, infections under simulated microgravity were more pathogenic. These findings highlight the potential for increased fungal virulence in space and underscore the need to understand microbial risks for astronaut health and safety in long-term space missions. IMPORTANCE Fungi have long been recognized for their remarkable ability to adapt to a wide range of environmental conditions, including extreme environments, such as space habitats. Understanding how fungal organisms, especially pathogenic fungi, adapt to these harsh conditions is crucial for gaining insight into their tolerance mechanisms and the potential emergence of virulence. Our research demonstrates that the pathogenic fungus Cryptococcus neoformans not only survives in space-like conditions but also exhibits increased stress tolerance, enhanced expression of key virulence factors, and elevated pathogenicity in animal models. These findings carry significant practical implications because concerns about fungal contamination in space or other extreme environments may be heightened by the potential for fungi to develop increased virulence through natural adaptation. Fungi have long been recognized for their remarkable ability to adapt to a wide range of environmental conditions, including extreme environments, such as space habitats. Understanding how fungal organisms, especially pathogenic fungi, adapt to these harsh conditions is crucial for gaining insight into their tolerance mechanisms and the potential emergence of virulence. Our research demonstrates that the pathogenic fungus Cryptococcus neoformans not only survives in space-like conditions but also exhibits increased stress tolerance, enhanced expression of key virulence factors, and elevated pathogenicity in animal models. These findings carry significant practical implications because concerns about fungal contamination in space or other extreme environments may be heightened by the potential for fungi to develop increased virulence through natural adaptation.