Microbial quest for food in vivo : ‘Nutritional virulence’ as an emerging paradigm: Microbial nutritional virulence
Open accessAbstract
Microbial access to host nutrients is a fundamental aspect of infectious diseases. Pathogens face complex dynamic nutritional host microenvironments that change with increasing inflammation and local hypoxia. Since the host can actively limit microbial access to nutrient supply, pathogens have evolved various metabolic adaptations to successfully exploit available host nutrients for proliferation. Recent studies have unraveled an emerging paradigm that we propose to designate as 'nutritional virulence'. This paradigm is based on specific virulence mechanisms that target major host biosynthetic and degradation pathways (proteasomes, autophagy and lysosomes) or nutrient-rich sources, such as glutathione, to enhance host supply of limiting nutrients, such as cysteine. Although Cys is the most limiting cellular amino acid, it is a metabolically favourable source of carbon and energy for various pathogens that are auxotrophic for Cys but utilize idiosyncratic nutritional virulence strategies to generate a gratuitous supply of host Cys. Therefore, proliferation of some intracellular pathogens is restricted by a host nutritional rheostat regulated by certain limiting amino acids, and pathogens have evolved idiosyncratic strategies to short circuit the host nutritional rheostat. Deciphering mechanisms of microbial 'nutritional virulence' and metabolism in vivo will facilitate identification of novel microbialand host targets for treatment and prevention of infectious diseases. Host-pathogen synchronization of amino acid auxotrophy indicates that this nutritional synchronization has been a major driving force in the evolution of many intracellular bacterial pathogens.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
During infection, pathogens are capable of altering the battlefield to increase the abundance of potential Fe sources.
“During infection, pathogens are capable of altering the battlefield to increase the abundance of potential Fe sources.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [10]
The resulting inflammatory response includes the release of Lf from secondary granules contained with polymorphonuclear leukocytes (PMNs).
“The resulting inflammatory response includes the release of Lf from secondary granules contained with polymorphonuclear leukocytes (PMNs) [10, 21, 27].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McKinney, J. D., zu Bentrup, K. H., Muñoz‐Elías, E. J., Miczák, A., Chen, B., Chan, W.-T., Swenson, D. L., Sacchettini, J. C., Jacobs, W. R., & Russell, D. G. (2000) · Nature · doi:10.1038/35021074 · Cited by 1,361 · see citing works
Gut inflammation provides a respiratory electron acceptor for Salmonella
Winter, S., Thiennimitr, P., Winter, M. G., Butler, B. P., Huseby, D. L., Crawford, R. W., Russell, J. M., Bevins, C. L., Adams, L. G., Tsolis, R. M., et al. (2010) · Nature · doi:10.1038/nature09415 · Cited by 1,271 · see citing works
Host-Derived Nitrate Boosts Growth of <i>E. coli</i> in the Inflamed Gut
Winter, S. E., Winter, M. G., Xavier, M. N., Thiennimitr, P., Poon, V., Keestra, A. M., Laughlin, R. C., Gomez, G., Wu, J., Lawhon, S. D., et al. (2013) · Science · doi:10.1126/science.1232467 · Cited by 1,019 · see citing works
Active Starvation Responses Mediate Antibiotic Tolerance in Biofilms and Nutrient-Limited Bacteria
Nguyen, D. M., Joshi-Datar, A., Lepine, F. L., Bauerle, E., Olakanmi, O., Beer, K. D., McKay, G. A., Siehnel, R., Schafhauser, J., Wang, Y., et al. (2011) · Science · doi:10.1126/science.1211037 · Cited by 974 · see citing works
Interdependence of hypoxic and innate immune responses
Nizet, V., & Johnson, R. S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2607 · Cited by 708 · see citing works
The central role of glutathione in the pathophysiology of human diseases
Franco, R., Schoneveld, O., Pappa, A., & Panayiotidis, M. I. (2007) · Archives of Physiology and Biochemistry · doi:10.1080/13813450701661198 · Cited by 536 · see citing works
Raffatellu, M., George, M. D., Akiyama, Y., Hornsby, M. J., Nuccio, S.-P., Paixao, T. A., Butler, B. P., Chu, H., Santos, R. L., Berger, T., et al. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.03.011 · Cited by 525 · see citing works
Host cell-free growth of the Q fever bacterium Coxiella burnetii
Omsland, A., Cockrell, D. C., Howe, D., Fischer, E. R., Virtaneva, K. I., Sturdevant, D. E., Porcella, S. F., & Heinzen, R. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812074106 · Cited by 407 · see citing works
Carbon metabolism of intracellular bacterial pathogens and possible links to virulence
Eisenreich, W., Dandekar, T., Heesemann, J., & Goebel, W. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2351 · Cited by 397 · see citing works
Tattoli, I., Sorbara, M. T., Vuckovic, D., Ling, A., Soares, F., Carneiro, L. A. M., Yang, C., Emili, A., Philpott, D. J., & Girardin, S. E. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.04.012 · Cited by 367 · see citing works
Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis
Rohmer, L., Hocquet, D., & Miller, S. I. (2011) · Trends in Microbiology · doi:10.1016/j.tim.2011.04.003 · Cited by 364 · see citing works
Starr, T., Child, R., Wehrly, T. D., Hansen, B. T., Hwang, S., López-Otı́n, C., Virgin, H. W., & Celli, J. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2011.12.002 · Cited by 338 · see citing works
Impact of genome reduction on bacterial metabolism and its regulation
Yus, E., Maier, T., Michalodimitrakis, K., van Noort, V., Yamada, T., Chen, W.-H., Wodke, J. A. H., Güell, M., Martínez, S., Bourgeois, R., et al. (2009) · Science · doi:10.1126/science.1177263 · Cited by 327 · see citing works
Autophagy and the Immune System
Kuballa, P., Nolte, W. M., Castoreno, A. B., & Xavier, R. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074948 · Cited by 326 · see citing works
Failure of Amino Acid Homeostasis Causes Cell Death following Proteasome Inhibition
Suraweera, A., Münch, C., Hanssum, A., & Bertolotti, A. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.003 · Cited by 299 · see citing works
Deretic, V. P. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.10.006 · Cited by 294 · see citing works
Lopez, C. A., Winter, S., Rivera-Chávez, F., Byndloss, M. X., Poon, V., Nuccio, S., Tsolis, R. M., & Bäumler, A. J. (2012) · mBio · doi:10.1128/mbio.00143-12 · Cited by 242 · see citing works
Elwell, C. A., Jiang, S., Kim, J. H., Lee, A., Wittmann, T., Hanada, K., Melançon, P., & Engel, J. N. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002198 · Cited by 231 · see citing works
Host Proteasomal Degradation Generates Amino Acids Essential for Intracellular Bacterial Growth
Price, C. T. D., Al‐Quadan, T., Šantić, M., Rosenshine, I., & Kwaik, Y. A. (2011) · Science · doi:10.1126/science.1212868 · Cited by 217 · see citing works
The 26S proteasome: assembly and function of a destructive machine
Gallastegui, N., & Groll, M. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.005 · Cited by 201 · see citing works
Adult Amino Acid Requirements: The Case for a Major Revision in Current Recommendations
Young, V. R. (1994) · Journal of Nutrition · doi:10.1093/jn/124.suppl_8.1517s · Cited by 178 · see citing works
Parallel Exploitation of Diverse Host Nutrients Enhances Salmonella Virulence
Steeb, B., Claudi, B., Burton, N. A., Tienz, P., Schmidt, A., Farhan, H., Mazé, A., & Bumann, D. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003301 · Cited by 178 · see citing works
Self-citationOmsland, A., Sager, J., Nair, V., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212831109 · Cited by 169 · see citing works
Niu, H., Xiong, Q., Yamamoto, A., Hayashi, M., & Rikihisa, Y. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218674109 · Cited by 156 · see citing works
Alkhuder, K., Meibom, K. L., Dubail, I., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000284 · Cited by 134 · see citing works
Fuchs, T. M., Eisenreich, W., Heesemann, J., & Goebel, W. (2011) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00301.x · Cited by 128 · see citing works
Price, C. T. D., Al‐Quadan, T., Šantić, M., et al. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20100771 · Cited by 128 · see citing works
Antivirulence Genes: Insights into Pathogen Evolution through Gene Loss
Bliven, K. A., & Maurelli, A. T. (2012) · Infection and Immunity · doi:10.1128/iai.00740-12 · Cited by 125 · see citing works
A metabolic network approach for the identification and prioritization of antimicrobial drug targets
Chavali, A. K., D’Auria, K. M., Hewlett, E. L., Pearson, R. D., & Papin, J. A. (2012) · Trends in Microbiology · doi:10.1016/j.tim.2011.12.004 · Cited by 116 · see citing works
Subversion of cellular autophagy by Anaplasma phagocytophilum
Niu, H., Yamaguchi, M., & Rikihisa, Y. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.01068.x · Cited by 116 · see citing works
Sleeping with the Enemy: How Intracellular Pathogens Cope with a Macrophage Lifestyle
Thi, E. P., Lambertz, U., & Reiner, N. E. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002551 · Cited by 96 · see citing works
Exploitation of evolutionarily conserved amoeba and mammalian processes by Legionella
Al‐Quadan, T., Price, C. T. D., & Kwaik, Y. A. (2012) · Trends in Microbiology · doi:10.1016/j.tim.2012.03.005 · Cited by 84 · see citing works
Chlamydia Species-Dependent Differences in the Growth Requirement for Lysosomes
Ouellette, S. P., Dorsey, F. C., Moshiach, S., Cleveland, J. L., & Carabeo, R. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016783 · Cited by 83 · see citing works
Francisella Tularensis Metabolism and its Relation to Virulence
Meibom, K. L., & Charbit, A. (2010) · Frontiers in Microbiology · doi:10.3389/fmicb.2010.00140 · Cited by 71 · see citing works
Prunier, A., Schuch, R., Fernández, R. E., et al. (2007) · Microbiology · doi:10.1099/mic.0.2007/006916-0 · Cited by 70 · see citing works
Bacterial catabolism of nonulosonic (sialic) acid and fitness in the gut
Almagro‐Moreno, S., & Boyd, E. F. (2010) · Gut Microbes · doi:10.4161/gmic.1.1.10386 · Cited by 62 · see citing works
Targeting of a Chlamydial Protease Impedes Intracellular Bacterial Growth
Christian, J. G., Heymann, J., Paschen, S. A., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002283 · Cited by 49 · see citing works
Al‐Quadan, T., Price, C. T. D., London, N., et al. (2011) · Trends in Microbiology · doi:10.1016/j.tim.2011.08.003 · Cited by 35 · see citing works
The Mycobacterium tuberculosis proteasome: more than just a barrel-shaped protease
Cerda-Maira, F. A., & Darwin, K. H. (2009) · Microbes and Infection · doi:10.1016/j.micinf.2009.08.003 · Cited by 34 · see citing works
Autophagosomes: A Fast-Food Joint for Unexpected Guests
Gutierrez, M. G., & Colombo, M. I. (2005) · Autophagy · doi:10.4161/auto.1.3.2063 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Strategies of intracellular pathogens for obtaining iron from the environment
Leon-Sicairos, N., Reyes-Cortes, R., Guadrón-Llanos, A. M., Madueña-Molina, J., Leon-Sicairos, C., & Canizalez-Román, A. (2015) · BioMed Research International · doi:10.1155/2015/476534 · Cited by 51 · see citing works
Chew, S. Y., Ho, K. L., Cheah, Y. K., Sandai, D., Brown, A. J. P., & Than, L. T. L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133172 · Cited by 40 · see citing works
Pérez, N., Johnson, R., Sen, B., & Ramakrishnan, G. (2016) · MicrobiologyOpen · doi:10.1002/mbo3.342 · Cited by 26 · see citing works
- Authors
- Abu Kwaik, Y., & Bumann, D.
- Affiliations
- Department of Microbiology and Immunology; College of Medicine; University of Louisville; Louisville; KY; 40202; USA
- University of Basel (CH)
- Corresponding author
- Bumann, Dirk
- ORCID
- Bumann, Dirk
- Venue
- Cellular Microbiology
- Publisher
- Wiley
- Published
- 2013-04-03
- Volume
- 15
- Issue
- 6
- Pages
- 882-890
- ISSN
- 1462-5814 (ISSN-L)
- OpenAlex
- W1587983189
- Cited by
- 182
- References
- 40
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 15 · 2023: 12 · 2022: 8 · 2021: 4 · 2020: 11 · 2019: 11 · 2018: 17 · 2017: 19 · 2016: 22 · 2015: 25 · 2014: 19 · 2013: 7
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- SystemsX.ch
- National Institute of Allergy and Infectious Diseases (R01 AI43965, R01AI043965, R01AI069321)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Keywords
- host-pathogen interaction, cysteine auxotrophy, glutathione, intracellular bacterial pathogens, limiting amino acids, proteasome, autophagy, lysosomes, hypoxia, inflammation
- MeSH terms
- Animals, Bacteria, Cysteine, Disease Models, Animal, Energy Metabolism, Glutathione, Humans, Microbiological Phenomena, Models, Biological, Nutritional Physiological Phenomena, Virulence, Mice, Host-Pathogen Interactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
