Cytokeratin 8 is an epithelial cell receptor for Pet, a cytotoxic serine protease autotransporter of Enterobacteriaceae.

Abstract:

UNLABELLED:The group of proteins known as serine protease autotransporters of Enterobacteriaceae (SPATE) is a growing family of serine proteases secreted to the external milieu by the type V secretion system. Pet toxin and some other SPATE belong to the class 1 cytotoxic SPATE, which have comparable protease strength on fodrin. Pet is internalized and is directed to its intracellular substrate by retrograde transport. However, the epithelial cell receptor for Pet has yet to be identified. We show that Pet has affinity for the epithelial cell surface until the saturation of the binding sites at 100 nM Pet. Affinity column assays and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis identified a cytokeratin (CK8) which directly binds to Pet, and both proteins colocalized on the cell surface. Interestingly, CK8 is not present in kidney cell lines, which are not susceptible to Pet. Inhibition experiments by using anti-CK8 and ck8 small interfering RNA (siRNA) blocked the cytotoxic effect induced by Pet, while exogenous CK8 expression in kidney cells made them susceptible to Pet intoxication. Recombinant CK8 showed a Pet-binding pattern similar to that seen by using fixed cells. Remarkably, Pet colocalized with CK8 and clathrin at early times (receptor-mediated endocytosis), and subsequently, Pet colocalized with CK8 and Rab5b in the early endosomes. These data support the idea that CK8 is an important receptor for Pet on epithelial cells for starting its cytotoxic effects. These data suggest that therapeutics that block Pet-CK8 interaction may improve outcome of diseases caused by Pet-secreting Enterobacteriaceae such as enteroaggregative Escherichia coli. IMPORTANCE:Receptor-ligand binding is one mechanism by which cells sense and respond to external cues. Receptors may also be utilized by toxins to mediate their own internalization. Pet toxin is secreted by enteroaggregative Escherichia coli, an organism that causes persistent diarrhea in children, traveler's diarrhea, and acute and persistent diarrhea in patients with HIV. Pet is a member of the family of serine protease autotransporters of Enterobacteriaceae (SPATE). SPATE in different pathogens are virulence factors, and Pet belongs to the class 1 cytotoxic SPATE, which have comparable protease strength on their biological substrate, fodrin (a cytoskeletal protein important for maintaining cell viability). To cleave fodrin, Pet enters the cells by clathrin-mediated endocytosis. This mechanism includes receptor-mediated endocytosis (a receptor-ligand complex triggers the endocytosis). We show that CK8 is an important receptor for Pet on epithelial cells and that it may be useful for identifying molecules that block the interaction of CK8 with Pet.

journal_name

mBio

journal_title

mBio

authors

Nava-Acosta R,Navarro-Garcia F

doi

10.1128/mBio.00838-13

subject

Has Abstract

pub_date

2013-12-10 00:00:00

pages

e00838-13

issue

6

issn

2150-7511

pii

mBio.00838-13

journal_volume

4

pub_type

杂志文章

相关文献

mBio文献大全
  • e-Biologics: Fabrication of Sustainable Electronics with "Green" Biological Materials.

    abstract::The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00695-17

    authors: Lovley DR

    更新日期:2017-06-27 00:00:00

  • Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation.

    abstract:UNLABELLED:The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA) signal transduction pathway. In this study, we ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01862-15

    authors: Geddes JM,Caza M,Croll D,Stoynov N,Foster LJ,Kronstad JW

    更新日期:2016-01-12 00:00:00

  • Quorum Sensing and Metabolic State of the Host Control Lysogeny-Lysis Switch of Bacteriophage T1.

    abstract::Bacterial viruses, or bacteriophages, are highly abundant in the biosphere and have a major impact on microbial populations. Many examples of phage interactions with their hosts, including establishment of dormant lysogenic and active lytic states, have been characterized at the level of the individual cell. However, ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01884-19

    authors: Laganenka L,Sander T,Lagonenko A,Chen Y,Link H,Sourjik V

    更新日期:2019-09-10 00:00:00

  • Combinatorial Loss of the Enzymatic Activities of Viral Uracil-DNA Glycosylase and Viral dUTPase Impairs Murine Gammaherpesvirus Pathogenesis and Leads to Increased Recombination-Based Deletion in the Viral Genome.

    abstract::Misincorporation of uracil or spontaneous cytidine deamination is a common mutagenic insult to DNA. Herpesviruses encode a viral uracil-DNA glycosylase (vUNG) and a viral dUTPase (vDUT), each with enzymatic and nonenzymatic functions. However, the coordinated roles of these enzymatic activities in gammaherpesvirus pat...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01831-18

    authors: Dong Q,Smith KR,Oldenburg DG,Shapiro M,Schutt WR,Malik L,Plummer JB,Mu Y,MacCarthy T,White DW,McBride KM,Krug LT

    更新日期:2018-10-30 00:00:00

  • Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus.

    abstract:UNLABELLED:Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. He...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01077-16

    authors: Ray A,Kinch LN,de Souza Santos M,Grishin NV,Orth K,Salomon D

    更新日期:2016-07-26 00:00:00

  • Cathelicidin Antimicrobial Peptides with Reduced Activation of Toll-Like Receptor Signaling Have Potent Bactericidal Activity against Colistin-Resistant Bacteria.

    abstract:UNLABELLED:The world is at the precipice of a postantibiotic era in which medical procedures and minor injuries can result in bacterial infections that are no longer effectively treated by antibiotics. Cathelicidins are peptides produced by animals to combat bacterial infections and to regulate innate immune responses....

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01418-16

    authors: Kao C,Lin X,Yi G,Zhang Y,Rowe-Magnus DA,Bush K

    更新日期:2016-09-20 00:00:00

  • Evolutionary landscape of the Mycobacterium tuberculosis complex from the viewpoint of PhoPR: implications for virulence regulation and application to vaccine development.

    abstract::Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of ...

    journal_title:mBio

    pub_type: 杂志文章,评审

    doi:10.1128/mBio.01289-15

    authors: Broset E,Martín C,Gonzalo-Asensio J

    更新日期:2015-10-20 00:00:00

  • Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation.

    abstract:UNLABELLED:Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replicat...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00258-16

    authors: Thornbrough JM,Jha BK,Yount B,Goldstein SA,Li Y,Elliott R,Sims AC,Baric RS,Silverman RH,Weiss SR

    更新日期:2016-03-29 00:00:00

  • Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus.

    abstract:UNLABELLED:In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particula...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01990-15

    authors: Carroll RK,Weiss A,Broach WH,Wiemels RE,Mogen AB,Rice KC,Shaw LN

    更新日期:2016-02-09 00:00:00

  • Nile red detection of bacterial hydrocarbons and ketones in a high-throughput format.

    abstract::A method for use in high-throughput screening of bacteria for the production of long-chain hydrocarbons and ketones by monitoring fluorescent light emission in the presence of Nile red is described. Nile red has previously been used to screen for polyhydroxybutyrate (PHB) and fatty acid esters, but this is the first r...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00109-11

    authors: Pinzon NM,Aukema KG,Gralnick JA,Wackett LP

    更新日期:2011-06-28 00:00:00

  • A Shift in Central Metabolism Accompanies Virulence Activation in Pseudomonas aeruginosa.

    abstract::The availability of energy has significant impact on cell physiology. However, the role of cellular metabolism in bacterial pathogenesis is not understood. We investigated the dynamics of central metabolism during virulence induction by surface sensing and quorum sensing in early-stage biofilms of the multidrug-resist...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02730-18

    authors: Perinbam K,Chacko JV,Kannan A,Digman MA,Siryaporn A

    更新日期:2020-03-10 00:00:00

  • UDP-4-Keto-6-Deoxyglucose, a Transient Antifungal Metabolite, Weakens the Fungal Cell Wall Partly by Inhibition of UDP-Galactopyranose Mutase.

    abstract::Can accumulation of a normally transient metabolite affect fungal biology? UDP-4-keto-6-deoxyglucose (UDP-KDG) represents an intermediate stage in conversion of UDP-glucose to UDP-rhamnose. Normally, UDP-KDG is not detected in living cells, because it is quickly converted to UDP-rhamnose by the enzyme UDP-4-keto-6-deo...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01559-17

    authors: Ma L,Salas O,Bowler K,Bar-Peled M,Sharon A

    更新日期:2017-11-21 00:00:00

  • Murine AKAP7 has a 2',5'-phosphodiesterase domain that can complement an inactive murine coronavirus ns2 gene.

    abstract::Viral 2',5'-phosphodiesterases (2',5'-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2',5'-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) s...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01312-14

    authors: Gusho E,Zhang R,Jha BK,Thornbrough JM,Dong B,Gaughan C,Elliott R,Weiss SR,Silverman RH

    更新日期:2014-07-01 00:00:00

  • The Pseudomonas aeruginosa PilSR Two-Component System Regulates Both Twitching and Swimming Motilities.

    abstract::Motility is an important virulence trait for many bacterial pathogens, allowing them to position themselves in appropriate locations at appropriate times. The motility structures type IV pili and flagella are also involved in sensing surface contact, which modulates pathogenicity. In Pseudomonas aeruginosa, the PilS-P...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01310-18

    authors: Kilmury SLN,Burrows LL

    更新日期:2018-07-24 00:00:00

  • The Unrecognized Threat of Secondary Bacterial Infections with COVID-19.

    abstract::Coronavirus disease 2019 (COVID-19) is the greatest pandemic of our generation, with 16 million people affected and 650,000 deaths worldwide so far. One of the risk factors associated with COVID-19 is secondary bacterial pneumonia. In recent studies on COVID-19 patients, secondary bacterial infections were significant...

    journal_title:mBio

    pub_type: 评论,杂志文章

    doi:10.1128/mBio.01806-20

    authors: Vaillancourt M,Jorth P

    更新日期:2020-08-07 00:00:00

  • Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii.

    abstract::The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00166-17

    authors: Chen Y,Farrer RA,Giamberardino C,Sakthikumar S,Jones A,Yang T,Tenor JL,Wagih O,Van Wyk M,Govender NP,Mitchell TG,Litvintseva AP,Cuomo CA,Perfect JR

    更新日期:2017-03-07 00:00:00

  • Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia.

    abstract::The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where t...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00884-14

    authors: Alagaili AN,Briese T,Mishra N,Kapoor V,Sameroff SC,Burbelo PD,de Wit E,Munster VJ,Hensley LE,Zalmout IS,Kapoor A,Epstein JH,Karesh WB,Daszak P,Mohammed OB,Lipkin WI

    更新日期:2014-02-25 00:00:00

  • Chromosome End Repair and Genome Stability in Plasmodium falciparum.

    abstract::The human malaria parasite Plasmodium falciparum replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack of efficient nonhom...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00547-17

    authors: Calhoun SF,Reed J,Alexander N,Mason CE,Deitsch KW,Kirkman LA

    更新日期:2017-08-08 00:00:00

  • Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection.

    abstract::Many Gram-negative bacterial pathogens require a type 3 secretion system (T3SS) to deliver effector proteins into eukaryotic cells. Contact of the tip complex of the T3SS with a target eukaryotic cell initiates secretion of the two bacterial proteins that assemble into the translocon pore in the plasma membrane. The t...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00877-19

    authors: Russo BC,Duncan JK,Goldberg MB

    更新日期:2019-05-28 00:00:00

  • Systematic CRISPR-Cas9-Mediated Modifications of Plasmodium yoelii ApiAP2 Genes Reveal Functional Insights into Parasite Development.

    abstract::Malaria parasites have a complex life cycle with multiple developmental stages in mosquito and vertebrate hosts, and different developmental stages express unique sets of genes. Unexpectedly, many transcription factors (TFs) commonly found in eukaryotic organisms are absent in malaria parasites; instead, a family of g...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01986-17

    authors: Zhang C,Li Z,Cui H,Jiang Y,Yang Z,Wang X,Gao H,Liu C,Zhang S,Su XZ,Yuan J

    更新日期:2017-12-12 00:00:00

  • Occurrence of cyclic di-GMP-modulating output domains in cyanobacteria: an illuminating perspective.

    abstract:UNLABELLED:Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical r...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00451-13

    authors: Agostoni M,Koestler BJ,Waters CM,Williams BL,Montgomery BL

    更新日期:2013-08-13 00:00:00

  • Proteins needed to activate a transcriptional response to the reactive oxygen species singlet oxygen.

    abstract:UNLABELLED:Singlet oxygen ((1)O(2)) is a reactive oxygen species generated by energy transfer from one or more excited donors to molecular oxygen. Many biomolecules are prone to oxidation by (1)O(2), and cells have evolved systems to protect themselves from damage caused by this compound. One way that the photosyntheti...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00541-12

    authors: Nam TW,Ziegelhoffer EC,Lemke RA,Donohue TJ

    更新日期:2013-01-08 00:00:00

  • A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides.

    abstract::Mucormycosis is an emerging lethal fungal infection in immunocompromised patients. Mucor circinelloides is a causal agent of mucormycosis and serves as a model system to understand genetics in Mucorales. Calcineurin is a conserved virulence factor in many pathogenic fungi, and calcineurin inhibition or deletion of the...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02949-19

    authors: Vellanki S,Billmyre RB,Lorenzen A,Campbell M,Turner B,Huh EY,Heitman J,Lee SC

    更新日期:2020-01-28 00:00:00

  • Offloading Role of a Discrete Thioesterase in Type II Polyketide Biosynthesis.

    abstract::Type II polyketides are a group of secondary metabolites with various biological activities. In nature, biosynthesis of type II polyketides involves multiple enzymatic steps whereby key enzymes, including ketoacyl-synthase (KSα), chain length factor (KSβ), and acyl carrier protein (ACP), are utilized to elongate the p...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01334-20

    authors: Hua K,Liu X,Zhao Y,Gao Y,Pan L,Zhang H,Deng Z,Jiang M

    更新日期:2020-09-15 00:00:00

  • Nitrite Derived from Endogenous Bacterial Nitric Oxide Synthase Activity Promotes Aerobic Respiration.

    abstract::Macrophage-derived nitric oxide (NO·) is a crucial effector against invading pathogens. Yet, paradoxically, several bacterial species, including some pathogens, are known to endogenously produce NO· via nitric oxide synthase (NOS) activity, despite its apparent cytotoxicity. Here, we reveal a conserved role for bacter...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00887-17

    authors: Chaudhari SS,Kim M,Lei S,Razvi F,Alqarzaee AA,Hutfless EH,Powers R,Zimmerman MC,Fey PD,Thomas VC

    更新日期:2017-08-01 00:00:00

  • Membrane Distribution of the Pseudomonas Quinolone Signal Modulates Outer Membrane Vesicle Production in Pseudomonas aeruginosa.

    abstract::The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule in Pseudomonas aeruginosa that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV) formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01034-17

    authors: Florez C,Raab JE,Cooke AC,Schertzer JW

    更新日期:2017-08-08 00:00:00

  • Septins arrange F-actin-containing fibers on the Chlamydia trachomatis inclusion and are required for normal release of the inclusion by extrusion.

    abstract::Chlamydia trachomatis is an obligate intracellular human pathogen that grows inside a membranous, cytosolic vacuole termed an inclusion. Septins are a group of 13 GTP-binding proteins that assemble into oligomeric complexes and that can form higher-order filaments. We report here that the septins SEPT2, -9, -11, and p...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01802-14

    authors: Volceanov L,Herbst K,Biniossek M,Schilling O,Haller D,Nölke T,Subbarayal P,Rudel T,Zieger B,Häcker G

    更新日期:2014-10-07 00:00:00

  • Low Polymerase Activity Attributed to PA Drives the Acquisition of the PB2 E627K Mutation of H7N9 Avian Influenza Virus in Mammals.

    abstract::Avian influenza viruses (AIVs) must acquire mammalian-adaptive mutations before they can efficiently replicate in and transmit among humans. The PB2 E627K mutation is known to play a prominent role in the mammalian adaptation of AIVs. The H7N9 AIVs that emerged in 2013 in China easily acquired the PB2 E627K mutation u...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01162-19

    authors: Liang L,Jiang L,Li J,Zhao Q,Wang J,He X,Huang S,Wang Q,Zhao Y,Wang G,Sun N,Deng G,Shi J,Tian G,Zeng X,Jiang Y,Liu L,Liu J,Chen P,Bu Z,Kawaoka Y,Chen H,Li C

    更新日期:2019-06-18 00:00:00

  • Large chromosomal rearrangements during a long-term evolution experiment with Escherichia coli.

    abstract:UNLABELLED:Large-scale rearrangements may be important in evolution because they can alter chromosome organization and gene expression in ways not possible through point mutations. In a long-term evolution experiment, twelve Escherichia coli populations have been propagated in a glucose-limited environment for over 25 ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01377-14

    authors: Raeside C,Gaffé J,Deatherage DE,Tenaillon O,Briska AM,Ptashkin RN,Cruveiller S,Médigue C,Lenski RE,Barrick JE,Schneider D

    更新日期:2014-09-09 00:00:00

  • Cyclic diguanylate signaling proteins control intracellular growth of Legionella pneumophila.

    abstract::Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell division, differentiation, and virulence. The role of cyclic diguanylate signaling in the lifestyle of Legionella pne...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00316-10

    authors: Levi A,Folcher M,Jenal U,Shuman HA

    更新日期:2011-01-11 00:00:00