Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions

被引：123
作者：
Tenor, JL
McCormick, BA
Ausubel, FM
Aballay, A [1 ]
机构：
[1] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[2] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Massachusetts Gen Hosp, Charlestown, MA 02129 USA
[3] Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA
[4] Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
来源：
CURRENT BIOLOGY | 2004年 / 14卷 / 11期
关键词：
D O I：
10.1016/j.cub.2004.05.050
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A Caenorhabditis elegans-Salmonella enterica host-pathogen model was used to identify both novel and previously known S. enterica virulence factors (HilA, HilD, InvH, SptP, RhuM, Spi4-F, PipA, VsdA, RepC, Sb25, RfaL, GmhA, LeuO, CstA, and RecC), including several related to the type III secretion system (TTSS) encoded in Salmonella pathogenicity island 1 (SPI-1). Mutants corresponding to presumptive novel virulence-related genes exhibited diminished ability to invade epithelial cells and/or to induce polymorphonuclear leukocyte migration in a tissue culture model of mammalian enteropathogenesis. When expressed in C. elegans intestinal cells, the S. enterica TTSS-exported effector protein SptP inhibited a conserved p38 MAPK signaling pathway and suppressed the diminished pathogenicity phenotype of an S. enterica sptP mutant. These results show that C. elegans is an attractive model to study the interaction between Salmonella effector proteins and components of the innate immune response, in part because there is a remarkable overlap between Salmonella virulence factors required for human and nematode pathogenesis.
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页码：1018 / 1024
页数：7
相关论文
共 35 条
[1]   Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans [J].
Aballay, A ;
Yorgey, P ;
Ausubel, FM .
CURRENT BIOLOGY, 2000, 10 (23) :1539-1542
[2]   Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing [J].
Aballay, A ;
Ausubel, FM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2735-2739
[3]   Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway [J].
Aballay, A ;
Drenkard, E ;
Hilbun, LR ;
Ausubel, FM .
CURRENT BIOLOGY, 2003, 13 (01) :47-52
[4]   hilA is a novel ompR/toxR family member that activates the expression of Salmonella typhimurium invasion genes [J].
Bajaj, V ;
Hwang, C ;
Lee, CA .
MOLECULAR MICROBIOLOGY, 1995, 18 (04) :715-727
[5]   The SPI-3 pathogenicity island of Salmonella enterica [J].
Blanc-Potard, AB ;
Solomon, F ;
Kayser, J ;
Groisman, EA .
JOURNAL OF BACTERIOLOGY, 1999, 181 (03) :998-1004
[6]   THE PLASMID-ENCODED YOP2B PROTEIN OF YERSINIA-PSEUDOTUBERCULOSIS IS A VIRULENCE DETERMINANT REGULATED BY CALCIUM AND TEMPERATURE AT THE LEVEL OF TRANSCRIPTION [J].
BOLIN, I ;
WOLFWATZ, H .
MOLECULAR MICROBIOLOGY, 1988, 2 (02) :237-245
[7]  
BORGONIE G, 1995, FUND APPL NEMATOL, V18, P227
[8]  
Brooke JS, 1996, J BIOL CHEM, V271, P3608
[9]   The Salmonella typhimurium InvH protein is an outer membrane lipoprotein required for the proper localization of InvG [J].
Daefler, S ;
Russel, M .
MOLECULAR MICROBIOLOGY, 1998, 28 (06) :1367-1380
[10]   EPITHELIAL-CELLS SECRETE THE CHEMOKINE INTERLEUKIN-8 IN RESPONSE TO BACTERIAL ENTRY [J].
ECKMANN, L ;
KAGNOFF, MF ;
FIERER, J .
INFECTION AND IMMUNITY, 1993, 61 (11) :4569-4574
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