Abstract:
:All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify cAMP as a key regulator that triggers the timely secretion of microneme proteins enabling receptor-engagement and invasion. We demonstrate that exposure of merozoites to a low K+ environment, typical of blood plasma, activates a bicarbonate-sensitive cytoplasmic adenylyl cyclase to raise cytosolic cAMP levels and activate protein kinase A, which regulates microneme secretion. We also show that cAMP regulates merozoite cytosolic Ca2+ levels via induction of an Epac pathway and demonstrate that increases in both cAMP and Ca2+ are essential to trigger microneme secretion. Our identification of the different elements in cAMP-dependent signaling pathways that regulate microneme secretion during invasion provides novel targets to inhibit blood stage parasite growth and prevent malaria.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Dawn A,Singh S,More KR,Siddiqui FA,Pachikara N,Ramdani G,Langsley G,Chitnis CEdoi
10.1371/journal.ppat.1004520subject
Has Abstractpub_date
2014-12-18 00:00:00pages
e1004520issue
12eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-14-00038journal_volume
10pub_type
杂志文章相关文献
PLoS Pathogens文献大全abstract::Mycoplasma pneumoniae, a human pathogenic bacterium, glides on host cell surfaces by a unique and unknown mechanism. It forms an attachment organelle at a cell pole as a membrane protrusion composed of surface and internal structures, with a highly organized architecture. In the present study, we succeeded in isolatin...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005299
更新日期:2015-12-03 00:00:00
abstract::Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression,...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008250
更新日期:2020-01-06 00:00:00
abstract::Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulatio...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004536
更新日期:2014-12-04 00:00:00
abstract::Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associa...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004498
更新日期:2014-11-06 00:00:00
abstract::The strain designated Chlamydia trachomatis serovar that was used for experiments in this paper is Chlamydia muridarum, a species closely related to C. trachomatis (and formerly termed the Mouse Pneumonitis strain of C. trachomatis. [corrected]. The obligate intracellular pathogen Chlamydia trachomatis replicates with...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002198
更新日期:2011-09-01 00:00:00
abstract::Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis. Here, we reporte...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007484
更新日期:2018-12-17 00:00:00
abstract::Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) is important for persistent infection in the host as well as viral oncogenesis. The replication and transcription activator (RTA) encoded by KSHV ORF50 plays a central role in the switch from viral latency to lytic replication. Given that RTA is a transcri...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008160
更新日期:2019-11-21 00:00:00
abstract::The success of Mycobacterium tuberculosis as a pathogen derives from its facile adaptation to the intracellular milieu of human macrophages. To explore this process, we asked whether adaptation also required interference with the metabolic machinery of the host cell. Temporal profiling of the metabolic flux, in cells ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004265
更新日期:2014-07-24 00:00:00
abstract::Human herpesviruses are antigenically rich agents that induce strong CD8+T cell responses in primary infection yet persist for life, continually challenging T cell memory through recurrent lytic replication and potentially influencing the spectrum of antigen-specific responses. Here we describe the first lytic proteom...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007110
更新日期:2018-09-24 00:00:00
abstract::The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2alpha) to inhibit protein translation. A broad range of regulator...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000311
更新日期:2009-02-01 00:00:00
abstract::Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral a...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001150
更新日期:2010-10-14 00:00:00
abstract::The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000192
更新日期:2008-10-01 00:00:00
abstract::CD4(+) T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an exper...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001212
更新日期:2010-11-24 00:00:00
abstract::Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [P...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003211
更新日期:2013-03-01 00:00:00
abstract::Although the importance of humoral immunity to malaria has been established, factors that control antibody production are poorly understood. Follicular helper T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody responses. While it has been proposed that expansion of antigen-specific Tfh c...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006484
更新日期:2017-07-10 00:00:00
abstract::Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5'-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quater...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005451
更新日期:2016-02-19 00:00:00
abstract::Future HIV vaccines are expected to induce effective Th1 cell-mediated and Env-specific antibody responses that are necessary to offer protective immunity to HIV infection. However, HIV infections are highly prevalent in helminth endemic areas. Helminth infections induce polarised Th2 responses that may impair HIV vac...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007182
更新日期:2018-07-26 00:00:00
abstract::Microbial pathogens often establish infection within particular niches of their host for replication. Determining how infection occurs preferentially in specific host tissues is a key aspect of understanding host-microbe interactions. Here, we describe the discovery of a natural microsporidian parasite of the nematode...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005724
更新日期:2016-06-30 00:00:00
abstract::In this study, we investigated the significance of a conserved five-amino acid motif 'AELPR' in the C-terminal region of helper component-proteinase (HCPro) for potato virus A (PVA; genus Potyvirus) infection. This motif is a putative interaction site for WD40 domain-containing proteins, including VARICOSE (VCS). We a...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008956
更新日期:2020-10-12 00:00:00
abstract::Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003052
更新日期:2012-01-01 00:00:00
abstract::Dengue virus (DENV) is an enveloped RNA virus that causes the most common arthropod-borne infection worldwide. The mechanism by which DENV infects the host cell remains unclear. In this work, we used live-cell imaging and single-virus tracking to investigate the cell entry, endocytic trafficking, and fusion behavior o...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000244
更新日期:2008-12-01 00:00:00
abstract::Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006019
更新日期:2016-11-30 00:00:00
abstract::Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleuk...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002363
更新日期:2011-11-01 00:00:00
abstract::Crohn's disease (CD) is a chronic inflammatory condition of diverse etiology. Exposure to foodborne pathogens causing acute gastroenteritis produces a long-term risk of CD well into the post-infectious period but the mechanistic basis for this ongoing relationship to disease onset is unknown. We developed two novel mo...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005907
更新日期:2016-10-06 00:00:00
abstract::Intracellular parasites, such as Leishmania spp, must acquire suitable carbon sources from the host cell in order to replicate. Here we present evidence that intracellular amastigote stages of Leishmania exploit amino sugars in the phagolysosome of mammalian macrophages as a source of carbon and energy. L. major paras...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001245
更新日期:2010-12-23 00:00:00
abstract::Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus that can give rise to cancers of both B-cell and epithelial cell origin. In EBV-induced cancers of epithelial origin, including nasopharyngeal carcinomas (NPCs) and gastric carcinomas, the latent EBV genome expresses very high levels of a cluster of 22 viral...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004979
更新日期:2015-06-12 00:00:00
abstract::Iron, an essential co-factor of respiratory chain proteins, is critical for mitochondrial function and maintenance of its redox balance. We previously reported a role for iron uptake in differentiation of Leishmania amazonensis into virulent amastigotes, by a mechanism that involves reactive oxygen species (ROS) produ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005340
更新日期:2016-01-07 00:00:00
abstract::Memory T cell inflation is a process in which a subset of cytomegalovirus (CMV) specific CD8 T cells continuously expands mainly during latent infection and establishes a large and stable population of effector memory cells in peripheral tissues. Here we set out to identify in vivo parameters that promote and limit CD...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007785
更新日期:2019-05-13 00:00:00
abstract::Antibody-dependent enhancement (ADE) of Ebola virus (EBOV) infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, l...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006139
更新日期:2016-12-30 00:00:00
abstract::Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, and infection control. However, our understanding of this crucial process is still rather limited because of experimental and conceptual challenges. Here, we used proteomics, microbial genetics,...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003301
更新日期:2013-01-01 00:00:00