The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice

被引:153
作者
Robertson, GT [1 ]
Roop, RM [1 ]
机构
[1] Louisiana State Univ, Med Ctr, Dept Microbiol & Immunol, Shreveport, LA 71130 USA
关键词
D O I
10.1046/j.1365-2958.1999.01629.x
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
Brucella abortus is a facultative intracellular pathogen that causes abortion and infertility in domestic animals and a severe debilitating febrile illness in humans. The mechanisms that this highly successful intracellular pathogen uses to adapt to, and survive within, the harsh intracellular environment of the host macrophage are presently unknown. Maintenance of the stationary phase growth state has been proposed to be critical for the virulence of several mammalian pathogens, but analysis of this relationship for the brucellae has not been undertaken. In order to evaluate this relationship, we examined the in vitro and in vivo characteristics of an isogenic hfq mutant constructed from virulent Brucella abortus 2308. In Escherichia coli, the hfq gene product is an RNA-binding protein that participates in the regulation of stationary phase stress resistance, at least partly by enhancing translation of the stationary phase-specific sigma factor RpoS. As expected, the Brucella abortus hfq mutant, designated Hfq3, showed increased sensitivity to H2O2, and decreased survival under acidic conditions (pH 4.0), during stationary phase growth compared with 2308. Hfq3 was also less able to withstand prolonged starvation than 2308. The Brucella abortus hfq mutant, unlike its parental strain 2308, fails to replicate in cultured murine macrophages, and is rapidly cleared from the spleens and livers of experimentally infected BALB/c mice. These findings suggest that the Brucella abortus hfq gene product makes an essential contribution to pathogenesis in mice, probably by allowing the brucellae to adapt appropriately to the harsh environmental conditions encountered within the host macrophage.
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收藏
页码:690 / 700
页数:11
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共 59 条
  • [11] Deletion of purE attenuates Brucella melitensis infection in mice
    Crawford, RM
    VandeVerg, L
    Yuan, L
    Hadfield, TL
    Warren, RL
    Drazek, ES
    Houng, HSH
    Hammack, C
    Sasala, K
    Polsinelli, T
    Thompson, J
    Hoover, DL
    [J]. INFECTION AND IMMUNITY, 1996, 64 (06) : 2188 - 2192
  • [12] Promoter substitution and deletion analysis of upstream region required for rpoS translational regulation
    Cunning, C
    Brown, L
    Elliott, T
    [J]. JOURNAL OF BACTERIOLOGY, 1998, 180 (17) : 4564 - 4570
  • [13] De Iannino NI, 1998, J BACTERIOL, V180, P4392
  • [14] The complete genome of the hyperthermophilic bacterium Aquifex aeolicus
    Deckert, G
    Warren, PV
    Gaasterland, T
    Young, WG
    Lenox, AL
    Graham, DE
    Overbeek, R
    Snead, MA
    Keller, M
    Aujay, M
    Huber, R
    Feldman, RA
    Short, JM
    Olsen, GJ
    Swanson, RV
    [J]. NATURE, 1998, 392 (6674) : 353 - 358
  • [15] The modified nucleoside 2-methylthio-N-6-isopentenyladenosine in tRNA of Shigella flexneri is required for expression of virulence genes
    Durand, JMB
    Bjork, GR
    Kuwae, A
    Yoshikawa, M
    Sasakawa, C
    [J]. JOURNAL OF BACTERIOLOGY, 1997, 179 (18) : 5777 - 5782
  • [16] CHARACTERIZATION AND GENETIC COMPLEMENTATION OF A BRUCELLA-ABORTUS HIGH-TEMPERATURE-REQUIREMENT-A (HTRA) DELETION MUTANT
    ELZER, PH
    PHILLIPS, RW
    KOVACH, ME
    PETERSON, KM
    ROOP, RM
    [J]. INFECTION AND IMMUNITY, 1994, 62 (10) : 4135 - 4139
  • [17] The HtrA stress response protease contributes to resistance of Brucella abortus to killing by murine phagocytes
    Elzer, PH
    Phillips, RW
    Robertson, GT
    Roop, RM
    [J]. INFECTION AND IMMUNITY, 1996, 64 (11) : 4838 - 4841
  • [18] THE ALTERNATIVE SIGMA-FACTOR KATF (RPOS) REGULATES SALMONELLA VIRULENCE
    FANG, FC
    LIBBY, SJ
    BUCHMEIER, NA
    LOEWEN, PC
    SWITALA, J
    HARWOOD, J
    GUINEY, DG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (24) : 11978 - 11982
  • [19] WHOLE-GENOME RANDOM SEQUENCING AND ASSEMBLY OF HAEMOPHILUS-INFLUENZAE RD
    FLEISCHMANN, RD
    ADAMS, MD
    WHITE, O
    CLAYTON, RA
    KIRKNESS, EF
    KERLAVAGE, AR
    BULT, CJ
    TOMB, JF
    DOUGHERTY, BA
    MERRICK, JM
    MCKENNEY, K
    SUTTON, G
    FITZHUGH, W
    FIELDS, C
    GOCAYNE, JD
    SCOTT, J
    SHIRLEY, R
    LIU, LI
    GLODEK, A
    KELLEY, JM
    WEIDMAN, JF
    PHILLIPS, CA
    SPRIGGS, T
    HEDBLOM, E
    COTTON, MD
    UTTERBACK, TR
    HANNA, MC
    NGUYEN, DT
    SAUDEK, DM
    BRANDON, RC
    FINE, LD
    FRITCHMAN, JL
    FUHRMANN, JL
    GEOGHAGEN, NSM
    GNEHM, CL
    MCDONALD, LA
    SMALL, KV
    FRASER, CM
    SMITH, HO
    VENTER, JC
    [J]. SCIENCE, 1995, 269 (5223) : 496 - 512
  • [20] Franze de Fernandez M T, 1972, J Biol Chem, V247, P824