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<p>Integration of mitochondria with adenosine triphosphate (ATP) consumption in the cytosol is a critical process for brain and lung energy balance. In this sense, many studies have revealed the participation of creatine kinase (CK), pyruvate kinase (PK), and adenylate kinase (AK), enzymes belonging to the phosphotransfer network, in the pathophysiology of infectious diseases. In this sense, the aim of this study was to determine if the phosphotransfer circuit could be a pathway linked to the bioenergetics dysfunction during disseminated cryptococcosis. Brain and lung cultures were conducted to confirm the infection and tissue damage, revealing 1.1 × 10<sup>4</sup> and 2.9 × 10<sup>4</sup>&#xa0;CFU/g of tissue on day 20 post-infection, respectively. Brain and lung cytosolic CK activities were significantly decreased in rats experimentally infected with <i>Cryptococcus neoformans </i>var.<i> grubii</i> in comparison to the control group, while mitochondrial CK activities were significantly increased. AK activity in the brain and lung was significantly decreased in rats experimentally infected with <i>C. neoformans </i>var.<i> grubii</i> in comparison to the control group, while PK activity did not significantly differ between the groups. Brain ATP levels were significantly higher in rats experimentally infected with <i>C. neoformans </i>var.<i> grubii</i> in comparison to the control group, while reduced significantly in the lung. In summary, experimental infection with <i>C. neoformans </i>var. <i>grubii</i> inhibits important enzymes related to the synthesis and utilization of ATP, impairing the cellular energy equilibrium that contributed to the pathogenesis of cryptococcosis disease.</p>

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Disseminated cryptococcosis impairs cerebral and pulmonary phosphotransfer network in rats experimentally infected with Cryptococcus neoformans var. grubii: the impact on energy metabolism

  • 期刊论文

  • 发表日期：

    2025年9月25日

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  • Matheus Dellaméa Baldissera,
  • Maria Fernanda Biscarra Bortolotto Paz,
  • Laís Suarez da Silva de Oliveira,
  • Marina Machado Maurente,
  • Camila Eduarda Justen,
  • Bernardo Andrade Constantino,
  • Julia Salvagni Nicaretta,
  • Isabela Maraschin Vieira,
  • Jandora Lima Ortiz,
  • Mariana Cancian,
  • Marcelo Leite da Veiga,
  • Raquel Tusi Tamiosso

摘要

Integration of mitochondria with adenosine triphosphate (ATP) consumption in the cytosol is a critical process for brain and lung energy balance. In this sense, many studies have revealed the participation of creatine kinase (CK), pyruvate kinase (PK), and adenylate kinase (AK), enzymes belonging to the phosphotransfer network, in the pathophysiology of infectious diseases. In this sense, the aim of this study was to determine if the phosphotransfer circuit could be a pathway linked to the bioenergetics dysfunction during disseminated cryptococcosis. Brain and lung cultures were conducted to confirm the infection and tissue damage, revealing 1.1 × 104 and 2.9 × 104 CFU/g of tissue on day 20 post-infection, respectively. Brain and lung cytosolic CK activities were significantly decreased in rats experimentally infected with Cryptococcus neoformans var. grubii in comparison to the control group, while mitochondrial CK activities were significantly increased. AK activity in the brain and lung was significantly decreased in rats experimentally infected with C. neoformans var. grubii in comparison to the control group, while PK activity did not significantly differ between the groups. Brain ATP levels were significantly higher in rats experimentally infected with C. neoformans var. grubii in comparison to the control group, while reduced significantly in the lung. In summary, experimental infection with C. neoformans var. grubii inhibits important enzymes related to the synthesis and utilization of ATP, impairing the cellular energy equilibrium that contributed to the pathogenesis of cryptococcosis disease.