Simultaneous prevention of glutamine synthesis and high-affinity transport attenuates Salmonella typhimurium virulence
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In Salmonella typhimurium, transcription of the glnA gene (encoding glutamine synthetase) is under the control of the nitrogen-regulatory (ntr) system comprising the alternate sigma factor sigma54 (NtrA) and the two-component sensor-transcriptional activator pair NtrB and NtrC. The glnA, ntrB, and ntrC genes form an operon. We measured the virulence of S. typhimurium strains with nitrogen-regulatory mutations after intraperitoneal (i.p.) or oral inoculations of BALB/c mice. Strains with single mutations in glnA, ntrA, ntrB, or ntrC had i.p. 50% lethal doses (LD50s) of <10 bacteria, similar to the wild-type strain. However, a strain with a delta(glnA-ntrC) operon deletion had an i.p. LD50 of >10(5) bacteria, as did delta glnA ntrA and delta glnA ntrC strains, suggesting that glnA strains require an ntr-transcribed gene for full virulence. High-level transcription of the glutamine transport operon (glnHPQ) is dependent upon both ntrA and ntrC, as determined by glnHp-lacZ fusion measurements. Moreover, delta glnA glnH and delta glnA glnQ strains are attenuated, similar to delta glnA ntrA and delta glnA ntrC strains. These results reveal that access of S. typhimurium to host glutamine depends on the ntr system, which apparently is required for the transcription of the glutamine transport genes. The delta(glnA-ntrC) strain exhibited a reduced ability to survive within the macrophage cell line J774, identifying a potential host environment with low levels of glutamine. Finally, the delta(glnA-ntrC) strain, when inoculated at doses as low as 10 organisms, provided mice with protective immunity against challenge by the wild-type strain, demonstrating its potential use as a live vaccine.
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Glutamine transport enzymes are overexpressed by S. typhimurium in the presence of thymol in an attempt to increase the virulence of the bacteria.
“Some enzymes, such as those involved in glutamine transport, are overexpressed by S. typhimurium in the presence of thymol in an attempt to increase the virulence of the bacteria [84].”
From Effect of essential oils on pathogenic bacteria (2013) · cites this paper as [84]
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Effect of essential oils on pathogenic bacteria
Nazzaro, F., Fratianni, F., De Martino, L., Coppola, R., & De Feo, V. (2013) · Pharmaceuticals · doi:10.3390/ph6121451 · Cited by 2,186 · see citing works
“typhimurium in the presence of thymol in an attempt to increase the virulence of the bacteria [84].”
BackgroundIron deficiency accelerates Helicobacter pylori–induced carcinogenesis in rodents and humans
Noto, J. M., Gaddy, J. A., Lee, J. Y., Piazuelo, M. B., Friedman, D. B., Colvin, D. C., Romero-Gallo, J., Suarez, G., Loh, J., Slaughter, J. C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64373 · Cited by 178 · see citing works
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- Authors
- Klose, K. E., & Mekalanos, J. J.
- Affiliations
- Harvard University (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1997-02
- Volume
- 65
- Issue
- 2
- Pages
- 587-596
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC176100
- OpenAlex
- W2134995324
- Cited by
- 106
- References
- 58
- Citations by year
- 2026: 1 · 2025: 3 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 8 · 2012: 3
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI026289, F32AI009118, AI09118-03, AI-26289)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Keywords
- Salmonella typhimurium, bacterial virulence, glutamine synthetase, glnA gene, sigma54, ntrA, NtrB, NtrC, glutamine transport, attenuated strains, live attenuated vaccine, macrophage survival, protective immunity
- MeSH terms
- Animals, Base Sequence, Biological Transport, Female, Genes, Bacterial, Glutamine, Macrophages, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Nitrogen, Operon, Salmonella typhimurium, Transcription, Genetic, Virulence, Gene Expression Regulation, Bacterial, Mutagenesis, Insertional, Mice
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