Induction of signal transduction pathways related to the pathogenicity of &lt;i&gt;Cryptococcus neoformans&lt;/i&gt; in the host environment

Matsumoto, Yasuhiko; Azami, Saki; Shiga, Haruka; Nagamachi, Tae; Moriyama, Hikari; Yamashita, Yūki; Yoshikawa, Asami; Sugita, Takashi

doi:10.5582/ddt.2019.01047

“…In C. neoformans , the calcineurin pathway is involved in capsule production and melanin synthesis, which are responsible for evading host immunity 39 . A calcineurin-deficient strain of C. neoformans showed decreased pathogenicity against mice and silkworms 25 , 40 , 41 .…”

Section: Discussionmentioning

confidence: 99%

“…The present study also showed that the calcineurin pathway is involved in the pathogenicity of T. asahii against silkworms. The calcineurin in C. neoformans regulates gene expression via the dephosphorylation of the transcription factors 39 . Therefore, we assumed that the calcineurin in T. asahii also regulates the virulence-related gene expression.…”

Section: Discussionmentioning

confidence: 99%

Development of an efficient gene-targeting system for elucidating infection mechanisms of the fungal pathogen Trichosporon asahii

Matsumoto

¹

,

Nagamachi

²

,

Yoshikawa

³

et al. 2021

Sci Rep

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Trichosporon asahii is a pathogenic fungus that causes severe, deep-seated fungal infections in neutropenic patients. Elucidating the infection mechanisms of T. asahii based on genetic studies requires a specific gene-targeting system. Here, we established an efficient gene-targeting system in a highly pathogenic T. asahii strain identified using the silkworm infection model. By comparing the pathogenicity of T. asahii clinical isolates in a silkworm infection model, T. asahii MPU129 was identified as a highly pathogenic strain. Using an Agrobacterium tumefaciens-mediated gene transfer system, we obtained a T. asahii MPU129 mutant lacking the ku70 gene, which encodes the Ku70 protein involved in the non-homologous end-joining repair of DNA double-strand breaks. The ku70 gene-deficient mutant showed higher gene-targeting efficiency than the wild-type strain for constructing a mutant lacking the cnb1 gene, which encodes the beta-subunit of calcineurin. The cnb1 gene-deficient mutant showed reduced pathogenicity against silkworms compared with the parental strain. These results suggest that an efficient gene-targeting system in a highly pathogenic T. asahii strain is a useful tool for elucidating the molecular mechanisms of T. asahii infection.

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“…It is possible that the different responses observed was due to the different cell types used (A549 vs. BEAS-2B), but another possibility is that upper bronchial epithelial cells respond more effectively to acapsular (or a thinner capsule) cryptococcal cells compared to epithelial cells found in the lower alveolar epithelium. It has been shown that cryptococcal particles have a very small or no capsule upon inhalation, and rapidly induce capsular growth as they proceed down the airway ( 42 , 129 – 131 ). One final possibility stems from the limitations and drawbacks some researchers find in using the A549 cell line.…”

Section: Modeling Cryptococcal Infections and What Has Been Learnedmentioning

confidence: 99%

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

Normile

¹

,

Bryan

²

,

Poeta

³

2020

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Cryptococcus species are environmental fungal pathogens and the causative agents of cryptococcosis. Infection occurs upon inhalation of infectious particles, which proliferate in the lung causing a primary infection. From this primary lung infection, fungal cells can eventually disseminate to other organs, particularly the brain, causing lethal meningoencephalitis. However, in most cases, the primary infection resolves with the formation of a lung granuloma. Upon severe immunodeficiency, dormant cryptococcal cells will start proliferating in the lung granuloma and eventually will disseminate to the brain. Many investigators have sought to study the protective host immune response to this pathogen in search of host parameters that keep the proliferation of cryptococcal cells under control. The majority of the work assimilates research carried out using the primary infection animal model, mainly because a reactivation model has been available only very recently. This review will focus on anti-cryptococcal immunity in both the primary and reactivation models. An understanding of the differences in host immunity between the primary and reactivation models will help to define the key host parameters that control the infections and are important for the research and development of new therapeutic and vaccine strategies against cryptococcosis.

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“…In C. neoformans, the calcineurin pathway is involved in capsule production and melanin synthesis, which are responsible for evading host immunity 42 . A calcineurin-de cient strain of C. neoformans showed decreased pathogenicity against mice and silkworms 25,43,44 .…”

Section: Discussionmentioning

confidence: 99%

Development of an Efficient Gene-targeting System for Elucidating Infection Mechanisms of the Fungal Pathogen Trichosporon Asahii

Matsumoto

¹

,

Nagamachi

²

,

Yoshikawa

³

et al. 2021

Preprint

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Trichosporon asahii is a pathogenic fungus that causes severe, deep-seated fungal infections in neutropenic patients. Elucidating the infection mechanisms of T. asahii based on genetic studies requires a specific gene-targeting system. Here, we established an efficient gene-targeting system in a highly pathogenic T. asahii strain identified using the silkworm infection model. By comparing the pathogenicity of T. asahii clinical isolates in a silkworm infection model, T. asahii MPU129 was identified as a highly pathogenic strain. Using an Agrobacterium tumefaciens-mediated gene transfer system, we obtained a T. asahii MPU129 mutant lacking the ku70 gene, which encodes the Ku70 protein involved in the non-homologous end-joining repair of DNA double-strand breaks. The ku70 gene-deficient mutant showed higher gene-targeting efficiency than the wild-type strain for constructing a mutant lacking the cnb1 gene, which encodes the beta-subunit of calcineurin. The cnb1 gene-deficient mutant showed reduced pathogenicity against silkworms compared with the parental strain. These results suggest that an efficient gene-targeting system in a highly pathogenic T. asahii strain is a useful tool for elucidating the molecular mechanisms of T. asahii infection.

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Induction of signal transduction pathways related to the pathogenicity of <i>Cryptococcus neoformans</i> in the host environment

Cited by 8 publications

References 47 publications

Development of an efficient gene-targeting system for elucidating infection mechanisms of the fungal pathogen Trichosporon asahii

Development of an efficient gene-targeting system for elucidating infection mechanisms of the fungal pathogen Trichosporon asahii

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

Development of an Efficient Gene-targeting System for Elucidating Infection Mechanisms of the Fungal Pathogen Trichosporon Asahii

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