lac Repressor Is an Antivirulence Factor of Salmonella enterica: Its Role in the Evolution of Virulence in Salmonella
Open accessAbstract
The genus Salmonella includes many pathogens of great medical and veterinary importance. Bacteria belonging to this genus are very closely related to those belonging to the genus Escherichia. lacZYA operon and lacI are present in Escherichia coli, but not in Salmonella enterica. It has been proposed that Salmonella has lost lacZYA operon and lacI during evolution. In this study, we have investigated the physiological and evolutionary significance of the absence of lacI in Salmonella enterica. Using murine model of typhoid fever, we show that the expression of LacI causes a remarkable reduction in the virulence of Salmonella enterica. LacI also suppresses the ability of Salmonella enterica to proliferate inside murine macrophages. Microarray analysis revealed that LacI interferes with the expression of virulence genes of Salmonella pathogenicity island 2. This effect was confirmed by RT-PCR and Western blot analysis. Interestingly, we found that SBG0326 of Salmonella bongori is homologous to lacI of Escherichia coli. Salmonella bongori is the only other species of the genus Salmonella and it lacks the virulence genes of Salmonella pathogenicity island 2. Overall, our results demonstrate that LacI is an antivirulence factor of Salmonella enterica and suggest that absence of lacI has facilitated the acquisition of virulence genes of Salmonella pathogenicity island 2 in Salmonella enterica making it a successful systemic pathogen.
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The acquisition of the lactose operon by Salmonella reduces its virulence potential.
“However, the acquisition of the lactose operon by Salmonella reduces its virulence potential [59].”
From Characterization of virulence factors of Salmonella isolated from human stools and street food in urban areas of Burkina Faso (2021) · cites this paper as [59]
The Results (page unavailable) show reduced virulence in mice when S. enterica expresses LacI. The Introduction (page unavailable) distinguishes lacI, which encodes the repressor, from the lacZYA lactose operon. The paper does not show that acquisition of the operon itself reduces virulence. (LLM, conf=0.88)
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Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
Clustal W and Clustal X version 2.0
Larkin, M., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., López, R., et al. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm404 · Cited by 28,221 · see citing works
ExPASy: the proteomics server for in-depth protein knowledge and analysis
Gasteiger, E. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg563 · Cited by 5,602 · see citing works
Complete genome sequence of Salmonella enterica serovar Typhimurium LT2
McClelland, M., Sanderson, K. E., Spieth, J., Clifton, S. W., Latreille, P., Courtney, L., Porwollik, S., Ali, J., Dante, M., Du, F., et al. (2001) · Nature · doi:10.1038/35101614 · Cited by 1,838 · see citing works
Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.
Fields, P. I., Swanson, R. V., Haidaris, C. G., & Heffron, F. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.14.5189 · Cited by 1,114 · see citing works
Amann, E. P., Ochs, B., & Kj, A. (1988) · Gene · doi:10.1016/0378-1119(88)90440-4 · Cited by 1,045 · see citing works
A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence.
Miller, S. I., Kukral, A. M., & Mekalanos, J. J. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.13.5054 · Cited by 936 · see citing works
Shea, J. E., Hensel, M., Gleeson, C., & Holden, D. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.6.2593 · Cited by 787 · see citing works
Determining Divergence Times of the Major Kingdoms of Living Organisms with a Protein Clock
Doolittle, R. F., Feng, D.-F., Tsang, S., Cho, G., & Little, E. (1996) · Science · doi:10.1126/science.271.5248.470 · Cited by 581 · see citing works
Salmonella Pathogenicity Island 2-Dependent Evasion of the Phagocyte NADPH Oxidase
Vázquez‐Torres, A., Xu, Y., Jones‐Carson, J., Holden, D. W., Lucia, S. M., Dinauer, M. C., Mastroeni, P., & Fang, F. C. (2000) · Science · doi:10.1126/science.287.5458.1655 · Cited by 557 · see citing works
pathogenicity islands: big virulence in small packages
Marcus, S. L., Brumell, J. H., Pfeifer, C. G., & Finlay, B. B. (2000) · Microbes and Infection · doi:10.1016/s1286-4579(00)00273-2 · Cited by 468 · see citing works
Maurelli, A. T., Fernández, R. E., Bloch, C. A., Rode, C. K., & Fasano, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3943 · Cited by 457 · see citing works
Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin
Sokurenko, E. V., Чеснокова, В. Л., Dykhuizen, D. E., Ofek, I., Wu, X., Krogfelt, K. A., Struve, C., Schembri, M. A., & Hasty, D. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8922 · Cited by 373 · see citing works
Salmonella Pathogenicity Island 2
Hensel, M. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01935.x · Cited by 362 · see citing works
Chakravortty, D., Hansen-Wester, I., & Hensel, M. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011547 · Cited by 344 · see citing works
Self-citationLin, S.-Y., & Riggs, A. D. (1975) · Cell · doi:10.1016/0092-8674(75)90116-6 · Cited by 338 · see citing works
Gilbert, W., & Müller‐Hill, B. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.6.2415 · Cited by 306 · see citing works
Evolution of pathogenicity islands of Salmonella enterica
Hensel, M. (2004) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2004.06.025 · Cited by 305 · see citing works
Lin, S.-Y., & Riggs, A. D. (1972) · Journal of Molecular Biology · doi:10.1016/0022-2836(72)90184-2 · Cited by 303 · see citing works
Complement Evasion by Bacteria and Parasites
Joiner, K. A. (1988) · Annual Review of Microbiology · doi:10.1146/annurev.mi.42.100188.001221 · Cited by 292 · see citing works
lac repressor—Operator interaction
Riggs, A. D., Newby, R. F., & Bourgeois, S. (1970) · Journal of Molecular Biology · doi:10.1016/0022-2836(70)90144-0 · Cited by 283 · see citing works
The genetic basis of tetrathionate respiration in Salmonella typhimurium
Hensel, M., Hinsley, A. P., Nikolaus, T., Sawers, R. G., & Berks, B. C. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01345.x · Cited by 253 · see citing works
Stoebel, D. M., Dean, A. M., & Dykhuizen, D. E. (2008) · Genetics · doi:10.1534/genetics.107.085399 · Cited by 227 · see citing works
Use of mixed infections with strains to study virulence genes and their interactions in vivo
Beuzón, C. R., & Holden, D. W. (2001) · Microbes and Infection · doi:10.1016/s1286-4579(01)01496-4 · Cited by 210 · see citing works
Hensel, M., Shea, J. E., Raupach, B., Monack, D. M., Falkow, S., Gleeson, C., Kubo, T., & Holden, D. W. (1997) · Molecular Microbiology · doi:10.1046/j.1365-2958.1997.3271699.x · Cited by 176 · see citing works
The lactose repressor system: paradigms for regulation, allosteric behavior and protein folding
Wilson, C. J., Zhan, H., Swint‐Kruse, L., & Matthews, K. S. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6296-z · Cited by 171 · see citing works
Black holes, antivirulence genes, and gene inactivation in the evolution of bacterial pathogens
Maurelli, A. T. (2006) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2006.00526.x · Cited by 150 · see citing works
Nakata, N., Tobe, T., Fukuda, I., Suzuki, T., Komatsu, K., Yoshikawa, M., & Sasakawa, C. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb01707.x · Cited by 138 · see citing works
Formation of a novel surface structure encoded by Salmonella Pathogenicity Island 2
Chakravortty, D., Rohde, M., Jäger, L., Deiwick, J., & Hensel, M. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600676 · Cited by 127 · see citing works
Self-citationEswarappa, S. M., Panguluri, K. K., Hensel, M., & Chakravortty, D. (2008) · Microbiology · doi:10.1099/mic.0.2007/011114-0 · Cited by 105 · see citing works
Self-citationEPISOMIC ELEMENT IN A STRAIN OF SALMONELLA TYPHOSA
Falkow, S., & Baron, L. S. (1962) · Journal of Bacteriology · doi:10.1128/jb.84.3.581-589.1962 · Cited by 87 · see citing works
The protein burden oflac operon products
Koch, A. L. (1983) · Journal of Molecular Evolution · doi:10.1007/bf02102321 · Cited by 86 · see citing works
Ho, T. D., & Slauch, J. M. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.2.611-620.2001 · Cited by 75 · see citing works
Selective disadvantage of non-functional protein synthesis inEscherichia coli
Andrews, K. J., & Hegeman, G. D. (1976) · Journal of Molecular Evolution · doi:10.1007/bf01739257 · Cited by 57 · see citing works
Glycine Insertion in the Hinge Region of Lactose Repressor Protein Alters DNA Binding
Falcon, C. M., & Matthews, K. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.43.30849 · Cited by 55 · see citing works
Conflicting needs for a Salmonella hypervirulence gene in host and non‐host environments
Mouslim, C., Hilbert, F., Huang, H. V., & Groisman, E. A. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03070.x · Cited by 54 · see citing works
Gal‐Mor, O., Gibson, D. L., Baluta, D., Vallance, B. A., & Finlay, B. B. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000036 · Cited by 52 · see citing works
Lack of Evidence for Horizontal Transfer of the lac Operon into Escherichia coli
Stoebel, D. M. (2004) · Molecular Biology and Evolution · doi:10.1093/molbev/msi056 · Cited by 26 · see citing works
Falcão, D. P., Trabulsi, L. R., Hickman, F. W., & Farmer, J. J. (1975) · Journal of Clinical Microbiology · doi:10.1128/jcm.2.4.349-353.1975 · Cited by 20 · see citing works
Kohbata, S., Takahashi, M., & Yabuuchi, E. (1983) · Journal of Clinical Microbiology · doi:10.1128/jcm.18.4.920-925.1983 · Cited by 18 · see citing works
Laboratory Infection with a Lactose-Fermenting Strain of Salmonella typhi
Kunz, L. J., & Ewing, W. H. (1965) · Journal of Bacteriology · doi:10.1128/jb.89.6.1629-1629.1965 · Cited by 15 · see citing works
Cohen, S., Wylie, B. A., Sooka, A., & Koornhof, H. J. (1987) · Journal of Clinical Microbiology · doi:10.1128/jcm.25.8.1516-1518.1987 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [22]Riggs AD Newby RF Bourgeois S 1970 lac repressor—perator interaction. II. Effect of galactosides and other ligands. J Mol Biol 51 303 314 4320936
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Louwen, R., Staals, R. H. J., Endtz, H. P., van Baarlen, P., & John van der, O. O. S. T. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00039-13 · Cited by 246 · see citing works
Salmonella bongori Provides Insights into the Evolution of the Salmonellae
Fookes, M. C., Schroeder, G. N., Langridge, G. C., Blondel, C. J., Mammina, C., Connor, T. R., Seth-Smith, H. M. B., Vernikos, G. S., Robinson, K. S., Sanders, M. J., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002191 · Cited by 212 · see citing works
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Archetti, M., Scheuring, I., Hoffman, M., Frederickson, M. E., Pierce, N. E., & Yu, D. W. (2011) · Ecology Letters · doi:10.1111/j.1461-0248.2011.01697.x · Cited by 179 · see citing works
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Ilyas, B., Tsai, C. N., & Coombes, B. K. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00428 · 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
Salmonella entericaserovars Typhimurium and Typhi as model organisms
Garai, P., Gnanadhas, D. P., & Chakravortty, D. (2012) · Virulence · doi:10.4161/viru.21087 · Cited by 112 · see citing works
Self-citationLet the Right One In: A Microeconomic Approach to Partner Choice in Mutualisms
Archetti, M., Úbeda, F., Drew Fudenberg, B., Green, J., Pierce, N. E., & Yu, D. W. (2010) · The American Naturalist · doi:10.1086/657622 · Cited by 84 · see citing works
SalmonellaVaccine Vectors Displaying Delayed Antigen SynthesisInVivoTo Enhance Immunogenicity
Wang, S., Li, Y., Scarpellini, G., Kong, W., Shi, H., Baek, C.-H., Gunn, B. M., Wanda, S.-Y., Roland, K. L., Zhang, X., et al. (2010) · Infection and Immunity · doi:10.1128/iai.00444-10 · Cited by 72 · see citing works
Salmonellaas a vaccine delivery vehicle
Roland, K. L., & Brenneman, K. E. (2013) · Expert Review of Vaccines · doi:10.1586/14760584.2013.825454 · Cited by 58 · see citing works
Mthembu, T. P., Zishiri, O. T., & El Zowalaty, M. E. (2019) · Pathogens · doi:10.3390/pathogens8030124 · Cited by 56 · see citing works
Identification of Virulence Factors and Antibiotic Resistance Markers Using Bacterial Genomics
Bakour, S., Sankar, S. A., Rathored, J., Biagini, P., Raoult, D., & Fournier, P. (2016) · Future Microbiology · doi:10.2217/fmb.15.149 · Cited by 52 · see citing works
Nikiema, M. E. M., Kakou-ngazoa, S., Ky/Ba, A., Sylla, A., Bako, E., Addablah, A. Y. A., Ouoba, J. B., Sampo, E., Gnada, K., Zongo, O., et al. (2021) · BMC Microbiology · doi:10.1186/s12866-021-02398-6 · Cited by 47 · see citing works
Wang, S., Li, Y., Shi, H., Sun, W., Roland, K. L., & Curtiss, R. (2010) · Infection and Immunity · doi:10.1128/iai.00445-10 · Cited by 46 · see citing works
Wada, T., Tanabe, Y., & Kutsukake, K. (2011) · Journal of Bacteriology · doi:10.1128/jb.05441-11 · Cited by 43 · see citing works
Calhoun, L. N., & Kwon, Y. M. (2011) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2010.11.034 · Cited by 39 · see citing works
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Chakraborty, S., Chaudhuri, D., Balakrishnan, A., & Chakravortty, D. (2014) · Microbiology · doi:10.1099/mic.0.078998-0 · Cited by 18 · see citing works
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Shelburne, S. A., Sahasrobhajane, P., Suber, B., Keith, D. B., Davenport, M. T., Horstmann, N., Kumaraswami, M., Olsen, R. J., Brennan, R. G., & Musser, J. M. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07708.x · Cited by 16 · see citing works
Hwang, J. M., Mattei, L. M., Blanton, L. V., Meneely, P., & Okeke, I. N. (2010) · Infection and Immunity · doi:10.1128/iai.00014-10 · Cited by 14 · see citing works
Pei, Y., Parreira, V. R., Roland, K. L., Curtiss, R., & Prescott, J. F. (2014) · PubMed Central · Cited by 14 · see citing works
Jiang, L., Ni, Z., Wang, L., Feng, L., & Liu, B. (2014) · Current Microbiology · doi:10.1007/s00284-014-0720-7 · Cited by 9 · see citing works
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- Authors
- Eswarappa, S. M., Karnam, G., Nagarajan, A. G., Chakraborty, S., & Chakravortty, D.
- Affiliations
- Indian Institute of Science Bangalore (IN)
- Corresponding author
- Chakravortty, Dipshikha
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-06-04
- Volume
- 4
- Issue
- 6
- Pages
- e5789
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2686271
- OpenAlex
- W1999206316
- Cited by
- 36
- References
- 43
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 4 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 1 · 2012: 2
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Indian Institute of Science (191/MCB)
- Department of Biotechnology, Ministry of Science and Technology, India (DBT 197)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Keywords
- lac repressor, LacI, Salmonella enterica, virulence evolution, SPI-2, virulence gene expression, Salmonella bongori, typhoid fever, macrophage proliferation, Escherichia coli, gene loss
- MeSH terms
- Amino Acid Sequence, Animals, Disease Models, Animal, Macrophages, Mice, Inbred BALB C, Molecular Sequence Data, Repressor Proteins, Typhoid Fever, Virulence, Sequence Homology, Amino Acid, Evolution, Molecular, Salmonella enterica, Genomic Islands, Cell Proliferation, Mice
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