IpaD of Shigella flexneri is independently required for regulation of Ipa protein secretion and efficient insertion of IpaB and IpaC into host membranes

被引:110
作者
Picking, WL
Nishioka, H
Hearn, PD
Baxter, MA
Harrington, AT
Blocker, A
Picking, WD
机构
[1] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
关键词
D O I
10.1128/IAI.73.3.1432-1440.2005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Shigella flexneri causes human dysentery after invading the cells of the colonic epithelium. The best-studied effectors of Shigella entry into colonocytes are the invasion plasmid antigens IpaC and IpaB. These proteins are exported via a type III secretion system (TTSS) to form a pore in the host membrane that may allow the translocation of other effectors into the host cytoplasm. TTSS-mediated secretion of IpaD is also required for translocation pore formation, bacterial invasion, and virulence, but the mechanistic role of this protein is unclear. IpaD is also known to be involved in controlling Ipa protein secretion, but here it is shown that this activity can be separated from its requirement for cellular invasion. Amino acids 40 to 120 of IpaD are not essential for IpaD-dependent invasion; however, deletions in this region still lead to constitutive IpaB/IpaC secretion. Meanwhile, a central deletion causes only a partial loss of control of Ipa secretion but completely eliminates IpaD's invasion function, indicating that IpaD's role in invasion is not a direct outcome of its ability to control Ipa secretion. As shigellae expressing ipaD N-terminal deletion mutations have reduced contact-mediated hemolysis activity and are less efficient at introducing IpaB and IpaC into erythrocyte membranes, it is possible that IpaD is responsible for insertion of IpaB/IpaC pores into target cell membranes. While efficient insertion of IpaB/IpaC pores is needed for optimal invasion efficiency, it may be especially important for Ipa-dependent membrane disruption and thus for efficient vacuolar escape and intercellular spread.
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页码:1432 / 1440
页数:9
相关论文
共 39 条
[1]   MXID, AN OUTER-MEMBRANE PROTEIN NECESSARY FOR THE SECRETION OF THE SHIGELLA-FLEXNERI IPA INVASINS [J].
ALLAOUI, A ;
SANSONETTI, PJ ;
PARSOT, C .
MOLECULAR MICROBIOLOGY, 1993, 7 (01) :59-68
[2]   From flagellum assembly to virulence: the extended family of type III export chaperones [J].
Bennett, JCQ ;
Hughes, C .
TRENDS IN MICROBIOLOGY, 2000, 8 (05) :202-204
[3]   The tripartite type III secreton of Shigella flexneri inserts IpaB and IpaC into host membranes [J].
Blocker, A ;
Gounon, P ;
Larquet, E ;
Niebuhr, K ;
Cabiaux, V ;
Parsot, C ;
Sansonetti, P .
JOURNAL OF CELL BIOLOGY, 1999, 147 (03) :683-693
[4]   Type III secretion systems and bacterial flagella: Insights into their function from structural similarities [J].
Blocker, A ;
Komoriya, K ;
Aizawa, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (06) :3027-3030
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   A bacterial invasin induces macrophage apoptosis by binding directly to ICE [J].
Chen, YJ ;
Smith, MR ;
Thirumalai, K ;
Zychlinsky, A .
EMBO JOURNAL, 1996, 15 (15) :3853-3860
[7]   Protein-protein interactions in the assembly of Shigella flexneri invasion plasmid antigens IpaB and IpaC into protein complexes [J].
Davis, R ;
Marquart, ME ;
Lucius, D ;
Picking, WD .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1998, 1429 (01) :45-56
[8]   The structure of Yersinia pestis V-antigen, an essential virulence factor and mediator of immunity against plague [J].
Derewenda, U ;
Mateja, A ;
Devedjiev, Y ;
Routzahn, KM ;
Evdokimov, AG ;
Derewenda, ZS ;
Waugh, DS .
STRUCTURE, 2004, 12 (02) :301-306
[9]   Virulence role of V antigen of Yersinia pestis at the bacterial surface [J].
Fields, KA ;
Nilles, ML ;
Cowan, C ;
Straley, SC .
INFECTION AND IMMUNITY, 1999, 67 (10) :5395-5408
[10]   The V antigen of Pseudomonas aeruginosa is required for assembly of the functional PopB/PopD translocation pore in host cell membranes [J].
Goure, J ;
Pastor, A ;
Faudry, E ;
Chabert, J ;
Dessen, A ;
Attree, I .
INFECTION AND IMMUNITY, 2004, 72 (08) :4741-4750