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1.
Specialized secretion systems are used by many bacteria to deliver effector proteins into host cells that can either mimic or disrupt the function of eukaryotic factors. We found that the intracellular pathogens Legionella pneumophila and Coxiella burnetii use a type IV secretion system to deliver into eukaryotic cells a large number of different bacterial proteins containing ankyrin repeat homology domains called Anks. The L. pneumophila AnkX protein prevented microtubule-dependent vesicular transport to interfere with fusion of the L. pneumophila-containing vacuole with late endosomes after infection of macrophages, which demonstrates that Ank proteins have effector functions important for bacterial infection of eukaryotic host cells.  相似文献   

2.
Legionella pneumophila proliferates in environmental amoeba and human cells within the Legionella-containing vacuole (LCV). The exported AnkB F-box effector of L. pneumophila is anchored into the LCV membrane by host-mediated farnesylation. Here, we report that host proteasomal degradation of Lys(48)-linked polyubiquitinated proteins, assembled on the LCV by AnkB, generates amino acids required for intracellular bacterial proliferation. The severe defect of the ankB null mutant in proliferation within amoeba and human cells is rescued by supplementation of a mixture of amino acids or cysteine, serine, pyruvate, or citrate, similar to rescue by genetic complementation. Defect of the ankB mutant in intrapulmonary proliferation in mice is rescued upon injection of a mixture of amino acids or cysteine. Therefore, Legionella promotes eukaryotic proteasomal degradation to generate amino acids needed as carbon and energy sources for bacterial proliferation within evolutionarily distant hosts.  相似文献   

3.
After actively entering its host cells, the protozoan parasite Toxoplasma gondii resides in an intracellular vacuole that is completely unable to fuse with other endocytic or biosynthetic organelles. The fusion blocking requires entry of viable organisms but is irreversible: fusion competence of the vacuole is not restored if the parasite is killed after entry. The fusion block can be overcome, however, by altering the parasite's route of entry. Thus, phagocytosis of viable antibody-coated T. gondii by Chinese hamster ovary cells transfected with macrophage-lymphocyte Fc receptors results in the formation of vacuoles that are capable of both fusion and acidification. Phagocytosis and fusion appear to involve a domain of the Fc receptor cytoplasmic tail distinct from that required for localization at clathrin-coated pits. These results suggest that the mechanism of fusion inhibition is likely to reflect a modification of the vacuole membrane at the time of its formation, as opposed to the secretion of a soluble inhibitor by the parasite.  相似文献   

4.
Intracellular bacteria and parasites typically invade host cells through the formation of an internalization vacuole around the invading pathogen. Plasmodium sporozoites, the infective stage of the malaria parasite transmitted by mosquitoes, have an alternative mechanism to enter cells. We observed breaching of the plasma membrane of the host cell followed by rapid repair. This mode of entry did not result in the formation of a vacuole around the sporozoite, and was followed by exit of the parasite from the host cell. Sporozoites traversed the cytosol of several cells before invading a hepatocyte by formation of a parasitophorous vacuole, in which they developed into the next infective stage. Sporozoite migration through several cells in the mammalian host appears to be essential for the completion of the life cycle.  相似文献   

5.
Ultrastructural data on the protozoan Amoeba proteus support a model of membrane recycling. At systole the amoeba contractile vacuole fuses with the cell surface and expels its contents. Observations by electron microscopy indicate that, as the vacuole empties, its bounding membrane transforms into tiny (35 nanometers in diameter) vesicles, identical to the vesicles that segregate fluid and contribute to the diastolic vacuole.  相似文献   

6.
Rab guanosine triphosphatases (GTPases) regulate vesicle trafficking in eukaryotic cells by reversibly associating with lipid membranes. Inactive Rab GTPases are maintained in the cytosol by binding to GDP-dissociation inhibitor (GDI). It is believed that specialized proteins are required to displace GDI from Rab GTPases before Rab activation by guanosine diphosphate-guanosine 5'-triphosphate (GDP-GTP) exchange factors (GEFs). Here, we found that SidM from Legionella pneumophila could act as both GEF and GDI-displacement factor (GDF) for Rab1. Rab1 released from GDI was inserted into liposomal membranes and was used as a substrate for SidM-mediated nucleotide exchange. During host cell infection, recruitment of Rab1 to Legionella-containing vacuoles depended on the GDF activity of SidM. Thus, GDF and GEF activity can be promoted by a single protein, and GDF activity can coordinate Rab1 recruitment from the GDI-bound pool.  相似文献   

7.
Salmonella enterica causes a variety of diseases, including gastroenteritis and typhoid fever. The success of this pathogen depends on its capacity to proliferate within host cells in a membrane-bound compartment. We found that the Salmonella-containing vacuole recruited the plus-end-directed motor kinesin. Bacterial effector proteins translocated into the host cell by a type III secretion system antagonistically regulated this event. Among these effectors, SifA targeted SKIP, a host protein that down-regulated the recruitment of kinesin on the bacterial vacuole and, in turn, controlled vacuolar membrane dynamics.  相似文献   

8.
The bacterial pathogen Legionella pneumophila exploits host cell vesicle transport by transiently manipulating the activity of the small guanosine triphosphatase (GTPase) Rab1. The effector protein SidM recruits Rab1 to the Legionella-containing vacuole (LCV), where it activates Rab1 and then AMPylates it by covalently adding adenosine monophosphate (AMP). L. pneumophila GTPase-activating protein LepB inactivates Rab1 before its removal from LCVs. Because LepB cannot bind AMPylated Rab1, the molecular events leading to Rab1 inactivation are unknown. We found that the effector protein SidD from L. pneumophila catalyzed AMP release from Rab1, generating de-AMPylated Rab1 accessible for inactivation by LepB. L. pneumophila mutants lacking SidD were defective for Rab1 removal from LCVs, identifying SidD as the missing link connecting the processes of early Rab1 accumulation and subsequent Rab1 removal during infection.  相似文献   

9.
TLR11 activation of dendritic cells by a protozoan profilin-like protein   总被引:1,自引:0,他引:1  
Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens.  相似文献   

10.
Salmonella enterica, the cause of food poisoning and typhoid fever, induces actin cytoskeleton rearrangements and membrane ruffling to gain access into nonphagocytic cells, where it can replicate and avoid innate immune defenses. Here, we found that SopB, a phosphoinositide phosphatase that is delivered into host cells by a type III secretion system, was essential for the establishment of Salmonella's intracellular replicative niche. SopB mediated the formation of spacious phagosomes following bacterial entry and was responsible for maintaining high levels of phosphatidylinositol-three-phosphate [PtdIns(3)P] in the membrane of the bacteria-containing vacuoles. Absence of SopB caused a significant defect in the maturation of the Salmonella-containing vacuole and impaired bacterial intracellular growth.  相似文献   

11.
The regulation of natural populations of invertebrate hosts by viral, bacterial, protozoan, or helminth infections is discussed, using models that combine elements of conventional epidemiology (where the host population is assumed constant) with dynamic elements drawn from predator-prey studies; the apparent absence of acquired immunity in invertebrates simplifies the analysis. Highly pathogenic infections, with long-lived infective stages, tend to produce cyclic behavior in their host populations. The models give an explanation of the 9- to 10-year population cycles of the larch bud moth (Zeiraphera diniana) in the European Alps and suggest that microsporidian protozoan and baculovirus infections may be responsible for the 5- to 12-year population cycles observed in many temperate forest insects.  相似文献   

12.
Exposure to primaquine for 48 hours caused lesions in the exoerythrocytic stages of Plasmodium fallax grown in cultivated cells derived from embryonic turkey brain. The lesions appeared in the form of cytoplasmic vacuoles when viewed under the light microscope. The electron microscope revealed these vacuoles as swollen mitochondria readily identifiable by their typical protozoan cristae. Mitochondria of the host cell were unaffected.  相似文献   

13.
Trypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, evades the host immune response through the process of antigenic variation. The variant antigen, known as the variant surface glycoprotein (VSG), is anchored to the cell surface by a glycosyl phosphatidylinositol (GPI) structure that contains myristate (n-tetradecanoate) as its only fatty acid component. The utilization of heteroatom-containing analogs of myristate was studied both in a cell-free system and in vivo. Results indicated that the specificity of fatty acid incorporation depends on chain length rather than on hydrophobicity. One analog, 10-(propoxy)decanoic acid, was highly toxic to trypanosomes in culture although it is nontoxic to mammalian cells.  相似文献   

14.
Ultrastructural changes in both pathogen and host cells in the interaction between Puccinia striiformis and wheat cultivar (Libellula) with slow-rusting resistance were observed by transmission electron microscopy. Observations revealed marked changes in ultrastructure of both pathogen and host cells. In the pathogen respect, there were many vesicles appeared in the intercellular hyphae and gradually fused into bigger vacuoles, a number of fat drops and electron-dense granules accumulated, mitochondria became swollen and some of them degraded into vesicles, and the plasmalemma of intercellular hyphae became dark. In the haustoria, the cytoplasm degraded gradually and developed a vacuole in the center, fat drops increased, the extrahaustorial matrix widened with a great amount of electron-dense fibrillar and granular materials, and most of the haustoria died with in conjunction with the disappearance of fat drops and other organelles. Structural defense of the host, including formation of cell wall apposition, collar and papilla, occurred in the host respect. Host resistance expression and cytological features occurring in the slow-rusting resistance were discussed.  相似文献   

15.
Parasites have evolved a plethora of mechanisms to ensure their propagation and evade antagonistic host responses. The intracellular protozoan parasite Theileria is the only eukaryote known to induce uncontrolled host cell proliferation. Survival of Theileria-transformed leukocytes depends strictly on constitutive nuclear factor kappa B (NF-kappaB) activity. We found that this was mediated by recruitment of the multisubunit IkappaB kinase (IKK) into large, activated foci on the parasite surface. IKK signalosome assembly was specific for the transforming schizont stage of the parasite and was down-regulated upon differentiation into the nontransforming merozoite stage. Our findings provide insights into IKK activation and how pathogens subvert host-cell signaling pathways.  相似文献   

16.
To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in Plasmodium falciparum. We identified 400 putative erythrocyte-targeted proteins corresponding to approximately 8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across Plasmodium species has implications for the development of new antimalarials.  相似文献   

17.
Malaria is a devastating public health menace, killing over one million people every year and infecting about half a billion. Here it is shown that the protozoan Plasmodium gallinaceum, a close relative of the human malaria parasite Plasmodium falciparum, can develop in the fruit fly Drosophila melanogaster. Plasmodium gallinaceum ookinetes injected into the fly developed into sporozoites infectious to the vertebrate host with similar kinetics as seen in the mosquito host Aedes aegypti. In the fly, a component of the insect's innate immune system, the macrophage, can destroy Plasmodia. These experiments suggest that Drosophila can be used as a surrogate mosquito for defining the genetic pathways involved in both vector competence and part of the parasite sexual cycle.  相似文献   

18.
The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host immunity against the parasite.  相似文献   

19.
Larval growth rates of Heliconius butterflies do not closely parallel host plant choice, an indication that factors other than host plant chemistry are important in evolving host specificity. High growth rate in one species is correlated with reduction in number of palatable host species. This suggests a mechanism by which ecologically restricted species become progressively biochemically specialized.  相似文献   

20.
盐胁迫下胡杨和毛白杨叶细胞中的离子区隔化   总被引:1,自引:0,他引:1  
该文以抗盐的胡杨和盐敏感的毛白杨组培再生苗为实验材料,利用X--射线微区分析技术研究盐胁迫下(为期20d的盐处理)叶片各种类型细胞内主要元素Na+、Cl-、K+的分布情况,测定的细胞类型包括:①叶脉细胞(叶脉维管束导管、叶脉维管束内部和外部的薄壁细胞);②叶肉细胞(栅栏组织、海绵组织);③表皮细胞(上、下表皮细胞).结果表明,胡杨和毛白杨叶细胞对盐离子的区隔化有明显差异:与毛白杨相比,盐处理后的胡杨叶细胞不但具有较高的拒Na+能力,即将Na+贮存在质外体中,而且液泡区隔Na+的能力也强于毛白杨.在Cl-的区隔化方面,对照处理胡杨各种类型的细胞(包括叶脉、叶肉和表皮细胞)Cl-浓度都高于毛白杨,但在盐胁迫下,胡杨叶片的细胞壁、液泡甚至叶绿体中Cl-的含量都低于毛白杨,这是胡杨根细胞限制Cl-离子根冠运输的结果.盐处理使胡杨叶片各种类型细胞中的K+浓度降低;与胡杨不同,毛白杨叶片细胞中质外体的K+浓度下降,而液泡中的K+水平却相应提高,这是毛白杨细胞内K+重新分配的结果:由于盐处理后毛白杨液泡内积累了过多的Cl-,K+从细胞壁进入液泡,用以平衡液泡内Cl-积累所带来的负电荷.  相似文献   

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