DksA is Required for Intercellular Spread of Shigella Flexneri Via an RpoS-independent Mechanism

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2001 Aug 14

PMID 11500451

Citations 22

Authors

S A Mogull

L J Runyen-Janecky

M Hong

S M Payne

Affiliations

Soon will be listed here.

Abstract

Pathogenesis of Shigella flexneri is dependent on the ability of the bacterium to invade and spread within epithelial cells. In this study, we identified dksA as a gene necessary for intercellular spread in, but not invasion of, cultured cells. The S. flexneri dksA mutant exhibited sensitivity to acid and oxidative stress, in part due to an effect of DksA on production of RpoS. However, an S. flexneri rpoS mutant formed plaques on tissue culture monolayers, thus excluding DksA regulation of RpoS as the mechanism responsible for the inability of the dksA mutant to spread intercellularly. Intracellular analysis of the dksA mutant indicates that it survived and divided within the Henle cell cytoplasm, but the dksA mutant cells were elongated, and some exhibited filamentation in the intracellular environment. Some of the S. flexneri dksA mutant cells showed aberrant localization of virulence protein IcsA, which may inhibit spread between epithelial cells.

Citing Articles

The ancestral stringent response potentiator, DksA has been adapted throughout evolution to orchestrate the expression of metabolic, motility, and virulence pathways.

Cohen H, Adani B, Cohen E, Piscon B, Azriel S, Desai P Gut Microbes. 2021; 14(1):1997294.

PMID: 34923900 PMC: 8726615. DOI: 10.1080/19490976.2021.1997294.

DksA coordinates bile-mediated regulation of virulence-associated phenotypes in type three secretion system-positive .

Sofia M, Dziejman M Microbiology (Reading). 2020; 167(2).

PMID: 33332258 PMC: 8131029. DOI: 10.1099/mic.0.001006.

Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of : Emphasis on Selecting Targets for Virulence and Vaccine Design Studies.

Sen T, Verma N Genes (Basel). 2020; 11(3).

PMID: 32210046 PMC: 7141135. DOI: 10.3390/genes11030340.

Regulatory Hierarchies Controlling Virulence Gene Expression in and .

Dorman M, Dorman C Front Microbiol. 2018; 9:2686.

PMID: 30473684 PMC: 6237886. DOI: 10.3389/fmicb.2018.02686.

Guanosine tetraphosphate relieves the negative regulation of Salmonella pathogenicity island-2 gene transcription exerted by the AT-rich ssrA discriminator region.

Tapscott T, Kim J, Crawford M, Fitzsimmons L, Liu L, Jones-Carson J Sci Rep. 2018; 8(1):9465.

PMID: 29930310 PMC: 6013443. DOI: 10.1038/s41598-018-27780-9.

References

Bernardini M, Mounier J, DHauteville H, Sansonetti P . Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin. Proc Natl Acad Sci U S A. 1989; 86(10):3867-71. PMC: 287242. DOI: 10.1073/pnas.86.10.3867. View

Suh S, Woods D, Hassett D, West S, Ohman D . Effect of rpoS mutation on the stress response and expression of virulence factors in Pseudomonas aeruginosa. J Bacteriol. 1999; 181(13):3890-7. PMC: 93876. DOI: 10.1128/JB.181.13.3890-3897.1999. View

Fuller M, Streger S, Rothmel R, Mailloux B, Hall J, Onstott T . Development of a vital fluorescent staining method for monitoring bacterial transport in subsurface environments. Appl Environ Microbiol. 2000; 66(10):4486-96. PMC: 92329. DOI: 10.1128/AEM.66.10.4486-4496.2000. View

COYNAULT C, Norel F . Virulence and vaccine potential of Salmonella typhimurium mutants deficient in the expression of the RpoS (sigma S) regulon. Mol Microbiol. 1996; 22(1):149-60. DOI: 10.1111/j.1365-2958.1996.tb02664.x. View

Tuveson R . The interaction of a gene (nur) controlling near-UV sensitivity and the polA1 gene in strains of E. coli K12. Photochem Photobiol. 1981; 33(6):919-23. DOI: 10.1111/j.1751-1097.1981.tb05513.x. View

Sandlin R, Maurelli A . Establishment of unipolar localization of IcsA in Shigella flexneri 2a is not dependent on virulence plasmid determinants. Infect Immun. 1998; 67(1):350-6. PMC: 96317. DOI: 10.1128/IAI.67.1.350-356.1999. View

Van Den Bosch L, Manning P, Morona R . Regulation of O-antigen chain length is required for Shigella flexneri virulence. Mol Microbiol. 1997; 23(4):765-75. DOI: 10.1046/j.1365-2958.1997.2541625.x. View

Nickerson C, Curtiss 3rd R . Role of sigma factor RpoS in initial stages of Salmonella typhimurium infection. Infect Immun. 1997; 65(5):1814-23. PMC: 175223. DOI: 10.1128/iai.65.5.1814-1823.1997. View

Parish C . Fluorescent dyes for lymphocyte migration and proliferation studies. Immunol Cell Biol. 1999; 77(6):499-508. DOI: 10.1046/j.1440-1711.1999.00877.x. View

10.

Steinhauer J, Agha R, Pham T, Varga A, Goldberg M . The unipolar Shigella surface protein IcsA is targeted directly to the bacterial old pole: IcsP cleavage of IcsA occurs over the entire bacterial surface. Mol Microbiol. 1999; 32(2):367-77. DOI: 10.1046/j.1365-2958.1999.01356.x. View

11.

. Back to log phase: sigma S as a global regulator in the osmotic control of gene expression in Escherichia coli. Mol Microbiol. 1996; 21(5):887-93. DOI: 10.1046/j.1365-2958.1996.511405.x. View

12.

Lange R . Identification of a central regulator of stationary-phase gene expression in Escherichia coli. Mol Microbiol. 1991; 5(1):49-59. DOI: 10.1111/j.1365-2958.1991.tb01825.x. View

13.

Small P, BLANKENHORN D, Welty D, Zinser E, Slonczewski J . Acid and base resistance in Escherichia coli and Shigella flexneri: role of rpoS and growth pH. J Bacteriol. 1994; 176(6):1729-37. PMC: 205261. DOI: 10.1128/jb.176.6.1729-1737.1994. View

14.

Headley V, Payne S . Differential protein expression by Shigella flexneri in intracellular and extracellular environments. Proc Natl Acad Sci U S A. 1990; 87(11):4179-83. PMC: 54071. DOI: 10.1073/pnas.87.11.4179. View

15.

Lee I, Lin J, Hall H, Bearson B, FOSTER J . The stationary-phase sigma factor sigma S (RpoS) is required for a sustained acid tolerance response in virulent Salmonella typhimurium. Mol Microbiol. 1995; 17(1):155-67. DOI: 10.1111/j.1365-2958.1995.mmi_17010155.x. View

16.

Payne S, Niesel D, Peixotto S, Lawlor K . Expression of hydroxamate and phenolate siderophores by Shigella flexneri. J Bacteriol. 1983; 155(3):949-55. PMC: 217785. DOI: 10.1128/jb.155.3.949-955.1983. View

17.

Sansonetti P . Molecular and cellular biology of Shigella flexneri invasiveness: from cell assay systems to shigellosis. Curr Top Microbiol Immunol. 1992; 180:1-19. DOI: 10.1007/978-3-642-77238-2_1. View

18.

Kang P, Craig E . Identification and characterization of a new Escherichia coli gene that is a dosage-dependent suppressor of a dnaK deletion mutation. J Bacteriol. 1990; 172(4):2055-64. PMC: 208704. DOI: 10.1128/jb.172.4.2055-2064.1990. View

19.

Tuveson R, Jonas R . Genetic control of near-UV (300-400 NM) sensitivity independent of the recA gene in strains of Escherichia coli K12. Photochem Photobiol. 1979; 30(6):667-76. DOI: 10.1111/j.1751-1097.1979.tb07197.x. View

20.

Menard R, Dehio C, Sansonetti P . Bacterial entry into epithelial cells: the paradigm of Shigella. Trends Microbiol. 1996; 4(6):220-6. DOI: 10.1016/0966-842X(96)10039-1. View