An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection
Abstract Candida albicans, responsible for approximately 70% of all Candida infections, is a leading cause of invasive candidiasis and poses a significant global health threat. With the emergence of drug-resistant strains, mortality rates have reached a staggering 63.6% in severe cases, complicating...
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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| Series: | Cell Communication and Signaling |
| Online Access: | https://doi.org/10.1186/s12964-025-02306-9 |
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| author | Shuvechha Chakraborty Indumathi Palanikumar Yash Gune K. V. Venkatesh Karthik Raman Susan Idicula-Thomas |
| author_facet | Shuvechha Chakraborty Indumathi Palanikumar Yash Gune K. V. Venkatesh Karthik Raman Susan Idicula-Thomas |
| author_sort | Shuvechha Chakraborty |
| collection | DOAJ |
| description | Abstract Candida albicans, responsible for approximately 70% of all Candida infections, is a leading cause of invasive candidiasis and poses a significant global health threat. With the emergence of drug-resistant strains, mortality rates have reached a staggering 63.6% in severe cases, complicating treatment options and demanding the discovery of novel therapeutic targets. To address this pressing need, using a unique multidisciplinary approach, we attempted to identify some the critical metabolic pathways that can be targeted to modulate the virulence of CAL. Condition-specific genome-scale metabolic models (GSMMs), along with a novel integrated host-CAL model developed in this study, highlighted the central role of arginine (Arg) metabolism and uncovered ALT1, an arginine biosynthesis enzyme, as a critical metabolic vulnerability in CAL virulence. Heightened expression of arginine biosynthesis genes indicated that increased arginine synthesis mainly occurred through proline intermediates during host interaction. Significantly impaired virulence and in vivo pathogenicity of ALT1-deleted CAL highlighted the potential of targeting arginine metabolism as a novel strategy to combat antifungal resistance and underscored the power of integrating systems biology with experimental approaches in identifying new therapeutic targets. |
| format | Article |
| id | doaj-art-012cdce1ca2f4888a773e449c6c8671b |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-012cdce1ca2f4888a773e449c6c8671b2025-08-20T03:05:07ZengBMCCell Communication and Signaling1478-811X2025-08-0123111410.1186/s12964-025-02306-9An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infectionShuvechha Chakraborty0Indumathi Palanikumar1Yash Gune2K. V. Venkatesh3Karthik Raman4Susan Idicula-Thomas5Biomedical Informatics Centre, ICMR-National Institute for Research in Reproductive and Child HealthDepartment of Biotechnology, Bhupat Jyoti Mehta School of Biosciences, Indian Institute of Technology (IIT) MadrasBiomedical Informatics Centre, ICMR-National Institute for Research in Reproductive and Child HealthDepartment of Chemical Engineering, Indian Institute of Technology BombayCentre for Integrative Biology and Systems medicinE (IBSE), Wadhwani School of Data Science and AI, IIT MadrasBiomedical Informatics Centre, ICMR-National Institute for Research in Reproductive and Child HealthAbstract Candida albicans, responsible for approximately 70% of all Candida infections, is a leading cause of invasive candidiasis and poses a significant global health threat. With the emergence of drug-resistant strains, mortality rates have reached a staggering 63.6% in severe cases, complicating treatment options and demanding the discovery of novel therapeutic targets. To address this pressing need, using a unique multidisciplinary approach, we attempted to identify some the critical metabolic pathways that can be targeted to modulate the virulence of CAL. Condition-specific genome-scale metabolic models (GSMMs), along with a novel integrated host-CAL model developed in this study, highlighted the central role of arginine (Arg) metabolism and uncovered ALT1, an arginine biosynthesis enzyme, as a critical metabolic vulnerability in CAL virulence. Heightened expression of arginine biosynthesis genes indicated that increased arginine synthesis mainly occurred through proline intermediates during host interaction. Significantly impaired virulence and in vivo pathogenicity of ALT1-deleted CAL highlighted the potential of targeting arginine metabolism as a novel strategy to combat antifungal resistance and underscored the power of integrating systems biology with experimental approaches in identifying new therapeutic targets.https://doi.org/10.1186/s12964-025-02306-9 |
| spellingShingle | Shuvechha Chakraborty Indumathi Palanikumar Yash Gune K. V. Venkatesh Karthik Raman Susan Idicula-Thomas An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection Cell Communication and Signaling |
| title | An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection |
| title_full | An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection |
| title_fullStr | An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection |
| title_full_unstemmed | An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection |
| title_short | An integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in Candida albicans during host infection |
| title_sort | integrated systems biology approach establishes arginine biosynthesis as a metabolic weakness in candida albicans during host infection |
| url | https://doi.org/10.1186/s12964-025-02306-9 |
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