Life and death in a macrophage: role of the glyoxylate cycle in virulence
Open accessAbstract
Phagocytic cells of the innate immune system, such as macrophages and neutrophils, are a primary line of defense against microbial infections. Patients with defects in innate immunity, such as those with chronic granulomatous disease or neutropenia, are extremely sensitive to a variety of infections
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The macrophage phagosome is perhaps the most severe nutrient limitation that C. albicans encounters.
“Perhaps the most severe nutrient limitation that C. albicans encounters is upon engulfment into the macrophage phagosome (Lorenz and Fink, 2002).”
From A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance (2016) · cites this paper as Lorenz and Fink, 2002
The opening section describes the macrophage phagolysosome as devoid of key nutrients, and the fungi section reports a nutrient-related response in C. albicans after phagocytosis. The paper does not compare this limitation with others C. albicans encounters, so it does not establish that it is perhaps the most severe. (LLM, conf=0.84)
Experimental — accuracy not yet measuredC. albicans employs β-oxidation (POX1, FOX2, POT1), the glyoxylate cycle (ICL1, MLS1), and gluconeogenesis to generate glucose from fatty acids for growth.
“For example, C. albicans employs β-oxidation ( POX1 , FOX2 , POT1 ), the glyoxylate cycle ( ICL1 , MLS1 ), and gluconeogenesis to generate glucose from fatty acids for growth (31-36).”
From <i>Candida auris</i> metabolism and growth preferences in physiologically relevant skin-like conditions (2026) · cites this paper as [33]
The fungi section identifies ICL1 and MLS1 in C. albicans and reports that its ICL1 mutant cannot utilize C2 carbon sources. The Glyoxylate Cycle section explains how C2 compounds can enter gluconeogenesis to produce glucose for growth. The passages do not establish fatty acids as the starting material or identify POX1, FOX2, and POT1 as C. albicans β-oxidation genes. Page numbers were not provided. (LLM, conf=0.86)
Experimental — accuracy not yet measuredConsiderable progress has been made in identifying pathogen-specific pathways, such as the glyoxylate cycle, that enable survival in the face of carbon starvation.
“Considerable progress has been made in identifying pathogen-specific pathways, such as the glyoxylate cycle, that enable survival in the face of carbon starvation (Barelle et al., 2006; Ene et al., 2014; Lorenz and Fink, 2002).”
From A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance (2016) · cites this paper as Lorenz and Fink, 2002
Both conventional and alternative carbon metabolism allow C. albicans to grow in various nutrient sources.
“Taken together, both conventional and alternative carbon metabolism allow C. albicans to grow in various nutrient sources.”
From <i>Candida auris</i> metabolism and growth preferences in physiologically relevant skin-like conditions (2026) · cites this paper as [33]
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Cites
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“Similarly, iron uptake is required for full virulence in many species, including M. tuberculosis and C. albicans (2, 12, 18 ).”
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Research works printed but not linked: 4
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Boshoff, H. I. M., & Barry, C. E. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1065 · Cited by 448 · see citing works
Niche-specific regulation of central metabolic pathways in a fungal pathogen
Barelle, C. J., Priest, C. L., MacCallum, D. M., Gow, N. A. R., Odds, F. C., & Brown, A. J. P. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00676.x · Cited by 336 · see citing works
Ramírez, M. A., & Lorenz, M. C. (2007) · Eukaryotic Cell · doi:10.1128/ec.00372-06 · Cited by 174 · see citing works
Self-citationFood Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense
Luan, H. H., & Medzhitov, R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.013 · Cited by 130 · see citing works
Copping, V. M. S., Barelle, C. J., Hube, B., Gow, N. A. R., Brown, A. J. P., & Odds, F. C. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki088 · Cited by 113 · see citing works
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Martins, V. P., Dinamarco, T. M., Soriani, F. M., Tudella, V. G., Oliveira, S. C., Goldman, G. H., Curti, C., & Uyemura, S. A. (2011) · Eukaryotic Cell · doi:10.1128/ec.00194-10 · Cited by 64 · see citing works
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“Considerable progress has been made in identifying pathogen-specific pathways, such as the glyoxylate cycle, that enable survival in the face of carbon starvation (Barelle et al., 2006; Ene et al., 2014; Lorenz and Fink, 2002).”
Tripathi, A., Liverani, E., Tsygankov, A. Y., & Puri, S. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013413 · Cited by 56 · see citing works
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate
Mota, S., Alves, R., Carneiro, C., Silva, S., Brown, A. J., Istel, F., Kuchler, K., Sampaio, P., Casal, M., Henriques, M., et al. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00919 · Cited by 49 · see citing works
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The disruption of <i>JEN1</i> from <i>Candida albicans</i> impairs the transport of lactate
Soares-Silva, I., Paiva, S., Kötter, P., Entian, K.-D., & Casal, M. (2004) · Molecular Membrane Biology · doi:10.1080/09687860400011373 · Cited by 47 · see citing works
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Guedouari, H., Gergondey, R., Bourdais, A., Vanparis, O., Bulteau, A. L., Camadro, J. M., & Auchère, F. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.07.006 · Cited by 45 · see citing works
Nicklas, J. P., Deming, C., Lee-Lin, S., Conlan, S., Shen, Z., Blaustein, R. A., & Segre, J. A. (2026) · mBio · doi:10.1128/mbio.03117-25 · Cited by 8 · see citing works
“For example, Candida lusitaniae uses β-oxidation ( FOX2 ) and the glyoxy late cycle ( ICL1 ) to metabolize fatty acids as a carbon source to grow and transports acetyl-units with carnitine acetyl-transferase systems ( CAT2 ) (42).”
- Authors
- Lorenz, M. C., & Fink, G. R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- ORCID
- Fink, Gerald R.
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2002-10
- Volume
- 1
- Issue
- 5
- Pages
- 657-662
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC126751
- OpenAlex
- W2155341933
- Cited by
- 300
- References
- 2
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 16 · 2020: 16 · 2019: 16 · 2018: 8 · 2017: 13 · 2016: 12 · 2015: 18 · 2014: 19 · 2013: 14 · 2012: 7
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (5R01-GM35010, R01GM035010)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- glyoxylate cycle, macrophages, bacterial virulence, innate immunity, phagocytosis, chronic granulomatous disease, neutropenia, host-pathogen interaction, microbial infection
- MeSH terms
- Candida albicans, Candidiasis, Glyoxylates, Humans, Macrophages, Mycobacterium tuberculosis, Mycoses, Phagocytosis, Saccharomyces cerevisiae, Tuberculosis, Virulence
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