A response to iron involving carbon metabolism in the opportunistic fungal pathogen Candida albicans DOI Creative Commons
Ritu Garg,

Zhengkai Zhu,

Francisco Hernandez

и другие.

mSphere, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

ABSTRACT Iron (Fe) is an essential micronutrient, and during infection, the host attempts to starve pathogens of this vital element through a process known as nutritional immunity. Successful have evolved means evade attack, example being Candida albicans, most prevalent human fungal pathogen. When Fe-starved, C. albicans induces multiple pathways for Fe uptake using SEF1 trans-regulator, we now describe previously unrecognized effect on metabolism that occurs independent SEF1. Specifically, limitation leads inhibition pyruvate dehydrogenase (PDH) connecting glycolysis mitochondrial respiration. PDH inactivation involves loss LAT1 catalytic subunit harboring lipoic acid co-factor. Protein lipoylation Fe-S dependent process, lipoylated alpha-ketoglutarate also inhibited in Fe-starved . does not protect against inactivation, despite induction import genes, cellular levels drop dramatically chronic starvation. Such seen bakers’ yeast Saccharomyces cerevisiae In both species, glucose diverted toward pentose phosphate pathway (PPP) PPP production NADPH increased response low loss. Additionally, consumption lowered , non-PDH alternatives producing Ac-CoA are induced, including bypass fatty oxidation pathways. can adapt well effects micronutrient cell metabolism. IMPORTANCE We new Fe-starvation pathogen involving carbon Pyruvate central inactivated at post-translational level cells. Nevertheless, thrive by activating backup systems metabolizing glucose. Methods inhibit these compensatory may prove beneficial future anti-fungal strategies.

Язык: Английский

An Introduction to the Influence of Nutritional Factors on the Pathogenesis of Opportunist Fungal Pathogens in Humans DOI Creative Commons

Timothy Jong,

Colin M. Stack, Michelle C. Moffitt

и другие.

Pathogens, Год журнала: 2025, Номер 14(4), С. 335 - 335

Опубликована: Март 31, 2025

Fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans are opportunistic pathogens in humans. They usually infect individuals whose immune system is compromised due to either a primary infection, e.g., HIV/AIDS, or part of treatment for another condition, stem cell solid organ transplant. In hosts with weakened system, these fungi can cause life-threatening infections. Unlike true pathogens, do not have specific mechanisms overcome healthy host, requiring different approach understand how they infection. The ability adapt various environmental conditions, including the human critical virulence. humans, micronutrient metals, iron, sequestered reduce serum concentrations, which helps inhibit microbial growth. Other tissues may increase metal concentrations toxic levels prevent infection by pathogens. acquire detoxify nutrients, iron copper, from host essential establishment this review, role fungal nutrition will be discussed relation It focus on acquisition micronutrients, zinc, enables circumvent nutritional immunity.

Язык: Английский

Процитировано

0
A response to iron involving carbon metabolism in the opportunistic fungal pathogen Candida albicans DOI Creative Commons
Ritu Garg,

Zhengkai Zhu,

Francisco Hernandez

и другие.

mSphere, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

ABSTRACT Iron (Fe) is an essential micronutrient, and during infection, the host attempts to starve pathogens of this vital element through a process known as nutritional immunity. Successful have evolved means evade attack, example being Candida albicans, most prevalent human fungal pathogen. When Fe-starved, C. albicans induces multiple pathways for Fe uptake using SEF1 trans-regulator, we now describe previously unrecognized effect on metabolism that occurs independent SEF1. Specifically, limitation leads inhibition pyruvate dehydrogenase (PDH) connecting glycolysis mitochondrial respiration. PDH inactivation involves loss LAT1 catalytic subunit harboring lipoic acid co-factor. Protein lipoylation Fe-S dependent process, lipoylated alpha-ketoglutarate also inhibited in Fe-starved . does not protect against inactivation, despite induction import genes, cellular levels drop dramatically chronic starvation. Such seen bakers’ yeast Saccharomyces cerevisiae In both species, glucose diverted toward pentose phosphate pathway (PPP) PPP production NADPH increased response low loss. Additionally, consumption lowered , non-PDH alternatives producing Ac-CoA are induced, including bypass fatty oxidation pathways. can adapt well effects micronutrient cell metabolism. IMPORTANCE We new Fe-starvation pathogen involving carbon Pyruvate central inactivated at post-translational level cells. Nevertheless, thrive by activating backup systems metabolizing glucose. Methods inhibit these compensatory may prove beneficial future anti-fungal strategies.

Язык: Английский

Процитировано

0