Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite.

Abstract:

:Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interaction with host RBC receptors. RhopH complex comprises at least three proteins, which include RhopH3. RhopH3 is critical for the process of red blood cell (RBC) invasion as well as intraerythrocytic development of human malaria parasite Plasmodium falciparum It is phosphorylated at serine 804 (S804) in the parasite; however, it is unclear if phosphorylation regulates its function. To address this, a CRISPR-CAS9-based approach was used to mutate S804 to alanine (A) in P. falciparum Using this phosphomutant (R3_S804A) of RhopH3, we demonstrate that the phosphorylation of S804 is critical for host RBC invasion by the parasite but not for its intraerythrocytic development. Importantly, the phosphorylation of RhopH3 regulates its localization to the rhoptries and discharge from the parasite, which is critical for RBC invasion. We also identified P. falciparum CDPK1 (PfCDPK1) as a possible candidate kinase for RhopH3-S804 phosphorylation and found that it regulates RhopH3 secretion from the parasite. These findings provide novel insights into the role of phosphorylation in rhoptry release and invasion, which is poorly understood.IMPORTANCE Host cell invasion by the malaria parasite is critical for establishing infection in human host and is dependent on discharge of key ligands from organelles like rhoptry and microneme, and these ligands interact with host RBC receptors. In the present study, we demonstrate that phosphorylation of a key rhoptry protein, RhopH3, is critical for host invasion. Phosphorylation regulates its localization to rhoptries and discharge from the parasite.

journal_name

mBio

journal_title

mBio

authors

Ekka R,Gupta A,Bhatnagar S,Malhotra P,Sharma P

doi

10.1128/mBio.00166-20

subject

Has Abstract

pub_date

2020-10-06 00:00:00

issue

5

issn

2150-7511

pii

mBio.00166-20

journal_volume

11

pub_type

杂志文章

相关文献

mBio文献大全
  • Novel (p)ppGpp Binding and Metabolizing Proteins of Escherichia coli.

    abstract::The alarmone (p)ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p)ppGpp was discovered over 4 decades ago, (p)ppGpp binding proteins have not been systematically identi...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02188-17

    authors: Zhang Y,Zborníková E,Rejman D,Gerdes K

    更新日期:2018-03-06 00:00:00

  • Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak.

    abstract:UNLABELLED:The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to Jul...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00019-16

    authors: Kim Y,Cheon S,Min CK,Sohn KM,Kang YJ,Cha YJ,Kang JI,Han SK,Ha NY,Kim G,Aigerim A,Shin HM,Choi MS,Kim S,Cho HS,Kim YS,Cho NH

    更新日期:2016-03-01 00:00:00

  • Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable Haemophilus influenzae.

    abstract::Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the bacterial genome. This epigene...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01682-18

    authors: Brockman KL,Azzari PN,Branstool MT,Atack JM,Schulz BL,Jen FE,Jennings MP,Bakaletz LO

    更新日期:2018-09-18 00:00:00

  • Decreased, Deformed, Defective-How HIV-1 Vpu Targets Peroxisomes.

    abstract::Peroxisomes are found in essentially all eukaryotic cells and have been described as important hubs in innate sensing and the induction of type III interferons upon viral infection. Nevertheless, it remains poorly investigated how viral pathogens modulate biogenesis or function of peroxisomes to evade innate sensing a...

    journal_title:mBio

    pub_type: 评论,杂志文章

    doi:10.1128/mBio.00967-20

    authors: Hopfensperger K,Sauter D

    更新日期:2020-05-26 00:00:00

  • Candida albicans hypha formation and mannan masking of β-glucan inhibit macrophage phagosome maturation.

    abstract:UNLABELLED:Candida albicans is a major life-threatening human fungal pathogen in the immunocompromised host. Host defense against systemic Candida infection relies heavily on the capacity of professional phagocytes of the innate immune system to ingest and destroy fungal cells. A number of pathogens, including C. albic...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01874-14

    authors: Bain JM,Louw J,Lewis LE,Okai B,Walls CA,Ballou ER,Walker LA,Reid D,Munro CA,Brown AJ,Brown GD,Gow NA,Erwig LP

    更新日期:2014-12-02 00:00:00

  • Structural and Regulatory Changes in PBP4 Trigger Decreased β-Lactam Susceptibility in Enterococcus faecalis.

    abstract::Enterococcus faecalis strains resistant to penicillin and ampicillin are rare and have been associated with increases in quantities of low-affinity penicillin-binding protein 4 (PBP4) or with amino acid substitutions in PBP4. We report an E. faecalis strain (LS4828) isolated from a prosthetic knee joint that was subje...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00361-18

    authors: Rice LB,Desbonnet C,Tait-Kamradt A,Garcia-Solache M,Lonks J,Moon TM,D'Andréa ÉD,Page R,Peti W

    更新日期:2018-04-03 00:00:00

  • Twice-daily application of HIV microbicides alter the vaginal microbiota.

    abstract:UNLABELLED:Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased ...

    journal_title:mBio

    pub_type: 杂志文章,随机对照试验

    doi:10.1128/mBio.00370-12

    authors: Ravel J,Gajer P,Fu L,Mauck CK,Koenig SS,Sakamoto J,Motsinger-Reif AA,Doncel GF,Zeichner SL

    更新日期:2012-12-18 00:00:00

  • A Burkholderia pseudomallei colony variant necessary for gastric colonization.

    abstract:UNLABELLED:Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02462-14

    authors: Austin CR,Goodyear AW,Bartek IL,Stewart A,Sutherland MD,Silva EB,Zweifel A,Vitko NP,Tuanyok A,Highnam G,Mittelman D,Keim P,Schweizer HP,Vázquez-Torres A,Dow SW,Voskuil MI

    更新日期:2015-02-03 00:00:00

  • Phosphoregulation of Nap1 plays a role in septin ring dynamics and morphogenesis in Candida albicans.

    abstract:UNLABELLED:Nap1 has long been identified as a potential septin regulator in yeasts. However, its function and regulation remain poorly defined. Here, we report functional characterization of Nap1 in the human-pathogenic fungus Candida albicans. We find that deletion of NAP1 causes constitutive filamentous growth and ch...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00915-13

    authors: Huang ZX,Zhao P,Zeng GS,Wang YM,Sudbery I,Wang Y

    更新日期:2014-02-04 00:00:00

  • Host Cell S Phase Restricts Legionella pneumophila Intracellular Replication by Destabilizing the Membrane-Bound Replication Compartment.

    abstract::Legionella pneumophila grows within cells ranging from environmental amoebae to human macrophages. In spite of this conserved strategy of pathogenesis, identification of host factors that restrict L. pneumophila intracellular replication has not been extended outside components of the mammalian innate immune response....

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02345-16

    authors: de Jesús-Díaz DA,Murphy C,Sol A,Dorer M,Isberg RR

    更新日期:2017-08-22 00:00:00

  • Genome sequencing reveals a phage in Helicobacter pylori.

    abstract:UNLABELLED:Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, like...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00239-11

    authors: Lehours P,Vale FF,Bjursell MK,Melefors O,Advani R,Glavas S,Guegueniat J,Gontier E,Lacomme S,Alves Matos A,Menard A,Mégraud F,Engstrand L,Andersson AF

    更新日期:2011-11-15 00:00:00

  • Stress-Induced MazF-Mediated Proteins in Escherichia coli.

    abstract::Escherichia colimazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. By that means, under stress, the induced MazF generates a stress-induced translation machinery (STM) composed of MazF-processed mRNAs and selective ribosomes...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00340-19

    authors: Nigam A,Ziv T,Oron-Gottesman A,Engelberg-Kulka H

    更新日期:2019-03-26 00:00:00

  • Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion.

    abstract:UNLABELLED:Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the periphe...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02145-15

    authors: Song R,Koyuncu OO,Greco TM,Diner BA,Cristea IM,Enquist LW

    更新日期:2016-02-02 00:00:00

  • The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism.

    abstract::Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity....

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.03027-20

    authors: Reithuber E,Nannapaneni P,Rzhepishevska O,Lindgren AEG,Ilchenko O,Normark S,Almqvist F,Henriques-Normark B,Mellroth P

    更新日期:2020-12-15 00:00:00

  • Methane Seep Carbonates Host Distinct, Diverse, and Dynamic Microbial Assemblages.

    abstract:UNLABELLED:Marine methane seeps are globally distributed geologic features in which reduced fluids, including methane, are advected upward from the subsurface. As a result of alkalinity generation during sulfate-coupled methane oxidation, authigenic carbonates form slabs, nodules, and extensive pavements. These carbona...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01348-15

    authors: Case DH,Pasulka AL,Marlow JJ,Grupe BM,Levin LA,Orphan VJ

    更新日期:2015-12-22 00:00:00

  • Clathrin- and Arp2/3-independent endocytosis in the fungal pathogen Candida albicans.

    abstract:UNLABELLED:Clathrin-mediated endocytosis (CME) is conserved among eukaryotes and has been extensively analyzed at a molecular level. Here, we present an analysis of CME in the human fungal pathogen Candida albicans that shows the same modular structure as those in other fungi and mammalian cells. Intriguingly, C. albic...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00476-13

    authors: Epp E,Nazarova E,Regan H,Douglas LM,Konopka JB,Vogel J,Whiteway M

    更新日期:2013-08-27 00:00:00

  • Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling.

    abstract::Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02414-19

    authors: Li Y,Dong B,Wei Z,Silverman RH,Weiss SR

    更新日期:2019-11-12 00:00:00

  • Influenza virus resistance to human neutralizing antibodies.

    abstract::The human antibody repertoire has an exceptionally large capacity to recognize new or changing antigens through combinatorial and junctional diversity established at the time of V(D)J recombination and through somatic hypermutation. Influenza viruses exhibit a relentless capacity to escape the human antibody response ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00213-12

    authors: Crowe JE Jr

    更新日期:2012-07-31 00:00:00

  • HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation.

    abstract::The proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProteasome-degraded products are...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02221-19

    authors: Yang Y,Liu W,Hu D,Su R,Ji M,Huang Y,Shereen MA,Xu X,Luo Z,Zhang Q,Liu F,Wu K,Liu Y,Wu J

    更新日期:2020-10-27 00:00:00

  • Shigella sonnei O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation.

    abstract::Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; on...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02654-19

    authors: Watson JL,Sanchez-Garrido J,Goddard PJ,Torraca V,Mostowy S,Shenoy AR,Clements A

    更新日期:2019-12-17 00:00:00

  • Human claudin-8 and -14 are receptors capable of conveying the cytotoxic effects of Clostridium perfringens enterotoxin.

    abstract:UNLABELLED:Clostridium perfringens enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of m...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00594-12

    authors: Shrestha A,McClane BA

    更新日期:2013-01-15 00:00:00

  • EspC, an Autotransporter Protein Secreted by Enteropathogenic Escherichia coli, Causes Apoptosis and Necrosis through Caspase and Calpain Activation, Including Direct Procaspase-3 Cleavage.

    abstract:UNLABELLED:Enteropathogenic Escherichia coli (EPEC) has the ability to antagonize host apoptosis during infection through promotion and inhibition of effectors injected by the type III secretion system (T3SS), but the total number of these effectors and the overall functional relationships between these effectors durin...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00479-16

    authors: Serapio-Palacios A,Navarro-Garcia F

    更新日期:2016-06-21 00:00:00

  • Metagenomic and Metaproteomic Insights into Photoautotrophic and Heterotrophic Interactions in a Synechococcus Culture.

    abstract::Microbial photoautotroph-heterotroph interactions underlie marine food webs and shape ecosystem diversity and structure in upper ocean environments. Here, bacterial community composition, lifestyle preference, and genomic- and proteomic-level metabolic characteristics were investigated for an open ocean Synechococcus ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.03261-19

    authors: Zheng Q,Wang Y,Lu J,Lin W,Chen F,Jiao N

    更新日期:2020-02-18 00:00:00

  • HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain.

    abstract::Once HIV-1 enters a cell, the viral core is uncoated by a poorly understood mechanism and the HIV-1 genomic RNA is reverse transcribed into DNA. Host cell factors are essential for these processes, although very few reverse transcription complex binding host cell factors have been convincingly shown to affect uncoatin...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00316-18

    authors: Rawle DJ,Li D,Swedberg JE,Wang L,Soares DC,Harrich D

    更新日期:2018-03-27 00:00:00

  • SLC6A14 Is a Genetic Modifier of Cystic Fibrosis That Regulates Pseudomonas aeruginosa Attachment to Human Bronchial Epithelial Cells.

    abstract::Cystic fibrosis (CF) is caused by mutations in the CFTR gene and is associated with progressive and ultimately fatal infectious lung disease. There can be considerable variability in disease severity among individuals with the same CFTR mutations, and recent genome-wide association studies have identified secondary ge...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02073-17

    authors: Di Paola M,Park AJ,Ahmadi S,Roach EJ,Wu YS,Struder-Kypke M,Lam JS,Bear CE,Khursigara CM

    更新日期:2017-12-19 00:00:00

  • The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint.

    abstract::The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA duri...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01159-19

    authors: Sau S,Liefshitz B,Kupiec M

    更新日期:2019-06-11 00:00:00

  • Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in Saccharomyces cerevisiae.

    abstract::During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA rep...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00705-20

    authors: Arbel M,Bronstein A,Sau S,Liefshitz B,Kupiec M

    更新日期:2020-05-05 00:00:00

  • The ESCRT-Related ATPase Vps4 Is Modulated by Interferon during Herpes Simplex Virus 1 Infection.

    abstract::Interferons (IFNs) and autophagy are critical neuronal defenses against viral infection. IFNs alter neuronal autophagy by promoting the accumulation of IFN-dependent LC3-decorated autophagic structures, termed LC3 clusters. Here, we analyzed LC3 clusters in sensory ganglia following herpes simplex virus 1 (HSV-1) infe...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02567-18

    authors: Cabrera JR,Manivanh R,North BJ,Leib DA

    更新日期:2019-03-05 00:00:00

  • Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9.

    abstract::Adaptation to alternating CO2 concentrations is crucial for all organisms. Carbonic anhydrases-metalloenzymes that have been found in all domains of life-enable fixation of scarce CO2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carboni...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02211-16

    authors: Pohlers S,Martin R,Krüger T,Hellwig D,Hänel F,Kniemeyer O,Saluz HP,Van Dijck P,Ernst JF,Brakhage A,Mühlschlegel FA,Kurzai O

    更新日期:2017-01-31 00:00:00

  • Range Expansion and the Origin of USA300 North American Epidemic Methicillin-Resistant Staphylococcus aureus.

    abstract::The USA300 North American epidemic (USA300-NAE) clone of methicillin-resistant Staphylococcus aureus has caused a wave of severe skin and soft tissue infections in the United States since it emerged in the early 2000s, but its geographic origin is obscure. Here we use the population genomic signatures expected from th...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02016-17

    authors: Challagundla L,Luo X,Tickler IA,Didelot X,Coleman DC,Shore AC,Coombs GW,Sordelli DO,Brown EL,Skov R,Larsen AR,Reyes J,Robledo IE,Vazquez GJ,Rivera R,Fey PD,Stevenson K,Wang SH,Kreiswirth BN,Mediavilla JR,Arias CA

    更新日期:2018-01-02 00:00:00