Abstract:
:Helicobacter pylori (Hp) injects the CagA effector protein into host epithelial cells and induces growth factor-like signaling, perturbs cell-cell junctions, and alters host cell polarity. This enables Hp to grow as microcolonies adhered to the host cell surface even in conditions that do not support growth of free-swimming bacteria. We hypothesized that CagA alters host cell physiology to allow Hp to obtain specific nutrients from or across the epithelial barrier. Using a polarized epithelium model system, we find that isogenic ΔcagA mutants are defective in cell surface microcolony formation, but exogenous addition of iron to the apical medium partially rescues this defect, suggesting that one of CagA's effects on host cells is to facilitate iron acquisition from the host. Hp adhered to the apical epithelial surface increase basolateral uptake of transferrin and induce its transcytosis in a CagA-dependent manner. Both CagA and VacA contribute to the perturbation of transferrin recycling, since VacA is involved in apical mislocalization of the transferrin receptor to sites of bacterial attachment. To determine if the transferrin recycling pathway is involved in Hp colonization of the cell surface, we silenced transferrin receptor expression during infection. This resulted in a reduced ability of Hp to colonize the polarized epithelium. To test whether CagA is important in promoting iron acquisition in vivo, we compared colonization of Hp in iron-replete vs. iron-deficient Mongolian gerbils. While wild type Hp and ΔcagA mutants colonized iron-replete gerbils at similar levels, ΔcagA mutants are markedly impaired in colonizing iron-deficient gerbils. Our study indicates that CagA and VacA act in concert to usurp the polarized process of host cell iron uptake, allowing Hp to use the cell surface as a replicative niche.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Tan S,Noto JM,Romero-Gallo J,Peek RM Jr,Amieva MRdoi
10.1371/journal.ppat.1002050subject
Has Abstractpub_date
2011-05-01 00:00:00pages
e1002050issue
5eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-10-00302journal_volume
7pub_type
杂志文章相关文献
PLoS Pathogens文献大全abstract::Innate immune cells shape the host response to microbial pathogens. Here we elucidate critical differences in the molecular response of macrophages vs. dendritic cells (DCs) to Histoplasma capsulatum, an intracellular fungal pathogen of humans. It has long been known that macrophages are permissive for Histoplasma gro...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005749
更新日期:2016-07-26 00:00:00
abstract::HIV-1 strains harboring immune escape mutations can persist in circulation, but the impact of selection by multiple HLA alleles on population HIV-1 dynamics remains unclear. In Japan, HIV-1 Reverse Transcriptase codon 135 (RT135) is under strong immune pressure by HLA-B*51:01-restricted and HLA-B*52:01-restricted T ce...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1009177
更新日期:2020-12-28 00:00:00
abstract::Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions, caused by parasitic flatworms of the genus Schistosoma (subclass Digenea). Following major water development schemes in the 1980s, schistosomiasis has become an important parasitic disease of children living in...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000571
更新日期:2009-09-01 00:00:00
abstract::Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocy...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006706
更新日期:2017-10-30 00:00:00
abstract::The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses orig...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000590
更新日期:2009-09-01 00:00:00
abstract::Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, infects human neutrophils and inhibits mitochondria-mediated apoptosis. Bacterial factors involved in this process are unknown. In the present study, we screened a genomic DNA library of A. phagocytophilum for effectors of the type IV s...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000774
更新日期:2010-02-19 00:00:00
abstract::Viroporins are small transmembrane proteins with ion channel activities modulating properties of intracellular membranes that have diverse proviral functions. Hepatitis C virus (HCV) encodes a viroporin, p7, acting during assembly, envelopment and secretion of viral particles (VP). HCV p7 is released from the viral po...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006774
更新日期:2017-12-18 00:00:00
abstract::Members of the TRIpartite interaction Motif (TRIM) family of E3 ligases have been shown to exhibit antiviral activities. Here we report a near comprehensive screen for antiretroviral activities of 55 TRIM proteins (36 human, 19 mouse). We identified approximately 20 TRIM proteins that, when transiently expressed in HE...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0040016
更新日期:2008-02-08 00:00:00
abstract::SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells. Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase activity that reduces cellular dNTP to a level where reverse transcriptase cannot function, although alternative mechanisms have been proposed recently. Here, w...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005194
更新日期:2015-10-02 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::Negative-sense RNA viruses assemble large ribonucleoprotein (RNP) complexes that direct replication and transcription of the viral genome. Influenza virus RNPs contain the polymerase, genomic RNA and multiple copies of nucleoprotein (NP). During RNP assembly, monomeric NP oligomerizes along the length of the genomic R...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004826
更新日期:2015-04-13 00:00:00
abstract::Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candida...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004875
更新日期:2015-05-06 00:00:00
abstract::The role of Activation-Induced Cytidine Deaminase (AID) in somatic hypermutation and polyclonal antibody affinity maturation has not been shown for polyclonal responses in humans. We investigated whether AID induction in human B cells following H1N1pdm09 vaccination correlated with in-vivo antibody affinity maturation...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002920
更新日期:2012-09-01 00:00:00
abstract::Infection with Mycobacterium tuberculosis is one of the leading causes of death worldwide. Recognition of M. tuberculosis by pattern recognition receptors is crucial for activation of both innate and adaptive immune responses. In the present study, we demonstrate that nucleotide-binding oligomerization domain 2 (NOD2)...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0010034
更新日期:2005-11-01 00:00:00
abstract::Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated wit...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0030160
更新日期:2007-11-01 00:00:00
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...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004520
更新日期:2014-12-18 00:00:00
abstract::Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet+ CD4+ T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4+ T cells, but the underl...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008994
更新日期:2020-10-13 00:00:00
abstract::Two billion people are latently infected with Mycobacterium tuberculosis (Mtb). Mtb-infected macrophages are likely to be sequestered inside the hypoxic environments of the granuloma and differentiate into lipid-loaded macrophages that contain triacylglycerol (TAG)-filled lipid droplets which may provide a fatty acid-...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002093
更新日期:2011-06-01 00:00:00
abstract::My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006420
更新日期:2017-08-10 00:00:00
abstract::Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. Infections with M. abscessus are increasingly found in patients with chronic lung diseases, especially cystic fibrosis, and are often refractory to antibiotic therapy. M. abscessus has two...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005986
更新日期:2016-11-02 00:00:00
abstract::We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated fr...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0030064
更新日期:2007-05-04 00:00:00
abstract::Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentia...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006422
更新日期:2017-08-07 00:00:00
abstract::Staphylococcus aureus (SA) is the causative agent of both skin/soft tissue infections as well as invasive bloodstream infections. Though vaccines have been developed to target both humoral and T cell-mediated immune responses against SA, they have largely failed due to lack of protective efficacy. Group 1 CD1-restrict...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008443
更新日期:2020-04-28 00:00:00
abstract::Apicomplexans are obligate intracellular parasites that actively penetrate their host cells to create an intracellular niche for replication. Commitment to invasion is thought to be mediated by the rhoptries, specialized apical secretory organelles that inject a protein complex into the host cell to form a tight-junct...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003162
更新日期:2013-02-01 00:00:00
abstract::Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005227
更新日期:2015-10-20 00:00:00
abstract::Influenza is a major cause of mortality and morbidity worldwide. Despite numerous studies of the pathogenesis of influenza in humans and animal models the dynamics of infection and transmission in individual hosts remain poorly characterized. In this study, we experimentally modelled transmission using the H1N1pdm09 i...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008628
更新日期:2020-07-24 00:00:00
abstract::Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive an...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002243
更新日期:2011-09-01 00:00:00
abstract::Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that di...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001220
更新日期:2010-12-09 00:00:00
abstract::The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell-mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000392
更新日期:2009-04-01 00:00:00
abstract::The disease state of amebiasis, caused by Entamoeba histolytica, varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses. The virulence factors of the pathogen, and host defense mechanisms, contribute to the outcomes of infection; however, the underlying genetic factors, ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006882
更新日期:2018-03-19 00:00:00