DOI: 10.1046/j.1365-2958.2001.02230.x. A<i>Salmonella</i>inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization

ASalmonellainositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization

10.1046/j.1365-2958.2001.02230.x

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

A central feature ofSalmonellapathogenicity is the bacterium's ability to enter into non‐phagocytic cells. Bacterial internalization is the consequence of cellular responses characterized by Cdc42‐ and Rac‐dependent actin cytoskeleton rearrangements. These responses are triggered by the co‐ordinated function of bacterial proteins delivered into the host cell by a specialized protein secretion system termed type III. We report here that SopB, aSalmonellainositol polyphosphatase delivered to the host cell by this secretion system, mediates actin cytoskeleton rearrangements and bacterial entry in a Cdc42‐dependent manner. SopB exhibits overlapping functions with two other effectors of bacterial entry, the Rho family GTPase exchange factors SopE and SopE2. Thus,Salmonellastrains deficient in any one of these proteins can enter into cells at high efficiency, whereas a strain lacking all three effectors is completely defective for entry. Consistent with an important role for inositol phosphate metabolism inSalmonella‐induced cellular responses, a catalytically defective mutant of SopB failed to stimulate actin cytoskeleton rearrangements and bacterial entry. Furthermore, bacterial infection of intestinal cells resulted in a marked increase in Ins(1,4,5,6)P4, a consumption of InsP5and the activation of phospholipase C. In agreement with thein vivofindings, purified SopB specifically dephosphorylated InsP5to Ins(1,4,5,6)P4in vitro. Surprisingly, the inositol phosphate fluxes induced bySalmonellawere not caused exclusively by SopB. We show that the SopB‐independent inositol phosphate fluxes are the consequence of the SopE‐dependent activation of an endogenous inositol phosphatase. The ability ofSalmonellato stimulate Rho GTPases signalling and inositol phosphate metabolism through alternative mechanisms is an example of the remarkable ability of this bacterial pathogen to manipulate host cellular functions.

Bibliography

Zhou, D., Chen, L., Hernandez, L., Shears, S. B., & GalÃ¡n, J. E. (2001). ASalmonellainositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Molecular Microbiology, 39(2), 248â260. Portico.

Authors 5

Daoguo Zhou (first)
Li‐Mei Chen (additional)
Lorraine Hernandez (additional)
Stephen B. Shears (additional)
Jorge E. Galán (additional)

References 41 Referenced 328

10.1128/JB.182.8.2341-2344.2000
10.1016/S0955-0674(96)80068-8
10.1126/science.274.5295.2115
10.1046/j.1365-2958.1996.471410.x
10.1084/jem.189.9.1479
10.1042/bj3280075
10.1038/376527a0
10.1073/pnas.94.26.14456
10.1046/j.1365-2958.1998.00684.x
10.1038/45829
10.1016/s1369-5274(99)80008-3
10.1146/annurev.cellbio.12.1.221
10.1126/science.284.5418.1322 / Science / Type III secretion machines: bacterial devices for protein delivery into host cells by Galán J.E. (1999)
10.1073/pnas.86.16.6383
10.1111/j.1365-2958.1997.mmi525.x
10.1016/0003-2697(91)90534-Z
10.1126/science.279.5350.509
10.1016/S0092-8674(00)81442-7
10.1073/pnas.95.5.2574
10.4049/jimmunol.159.11.5550 / J Immunol / Involvement of the mitogen‐activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal cells by Hobbie S. (1997)
10.1038/291238a0
10.1016/S0092-8674(00)81540-8
10.1083/jcb.148.3.481
10.1093/emboj/17.21.6241
10.1111/j.1365-2958.1994.tb00450.x
10.1111/j.1365-2958.1996.tb02571.x
10.1074/jbc.273.46.30497
10.1016/S0960-9822(06)00423-4
10.1074/jbc.274.51.36790
10.1016/S0021-9258(18)55328-X
10.1073/pnas.95.24.14057
10.1007/978-3-642-58591-3_1
10.1016/s0014-5793(00)01194-7
10.1002/bies.950180109
10.1093/oso/9780199636396.001.0001 / Signalling by Inositides: a Practical Approach. by Shears S.B. (1997)
{'key': 'e_1_2_6_37_1', 'first-page': '109', 'article-title': 'Electron microscopic studies of experimental Salmonella infection. 1. Penetration into the intestinal epithelium by Salmonella typhimurium', 'volume': '50', 'author': 'Takeuchi A.', 'year': '1967', 'journal-title': 'Am J Pathol'} / Am J Pathol / Electron microscopic studies of experimental Salmonella infection. 1. Penetration into the intestinal epithelium by Salmonella typhimurium by Takeuchi A. (1967)
10.1042/bj3180561
10.1046/j.1365-2958.1996.00116.x
10.1074/jbc.271.39.23815 / J Biol Chem / Phosphatidylinositol 4,5‐biphosphate provides an alternative to guanine nucleotide exchange factors by stimulating the dissociation of GDP from CDC42Hs by Zheng Y. (1996)
10.1126/science.283.5410.2092
10.1073/pnas.96.18.10176

Dates

Type	When
Created	22 years, 5 months ago (March 12, 2003, 6:35 a.m.)
Deposited	1 year, 7 months ago (Jan. 3, 2024, 12:39 p.m.)
Indexed	2 days, 13 hours ago (Aug. 21, 2025, 12:43 p.m.)
Issued	24 years, 7 months ago (Jan. 1, 2001)
Published	24 years, 7 months ago (Jan. 1, 2001)
Published Online	23 years, 8 months ago (Dec. 21, 2001)
Published Print	24 years, 7 months ago (Jan. 1, 2001)

Funders 0

None

BibTeX

@article{Zhou_2001, title={ASalmonellainositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization}, volume={39}, ISSN={1365-2958}, url={http://dx.doi.org/10.1046/j.1365-2958.2001.02230.x}, DOI={10.1046/j.1365-2958.2001.02230.x}, number={2}, journal={Molecular Microbiology}, publisher={Wiley}, author={Zhou, Daoguo and Chen, Li‐Mei and Hernandez, Lorraine and Shears, Stephen B. and Galán, Jorge E.}, year={2001}, month=jan, pages={248–260} }

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