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Cell Host & Microbe

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https://www.readbyqxmd.com/read/30057173/a-phosphatidylinositol-3-kinase-effector-alters-phagosomal-maturation-to-promote-intracellular-growth-of-francisella
#1
Hannah E Ledvina, Katherine A Kelly, Aria Eshraghi, Rachael L Plemel, S Brook Peterson, Brian Lee, Shaun Steele, Marlen Adler, Thomas H Kawula, Alexey J Merz, Shawn J Skerrett, Jean Celli, Joseph D Mougous
Many pathogenic intracellular bacteria manipulate the host phago-endosomal system to establish and maintain a permissive niche. The fate and identity of these intracellular compartments is controlled by phosphoinositide lipids. By mechanisms that have remained undefined, a Francisella pathogenicity island-encoded secretion system allows phagosomal escape and replication of bacteria within host cell cytoplasm. Here we report the discovery that a substrate of this system, outside pathogenicity island A (OpiA), represents a family of wortmannin-resistant bacterial phosphatidylinositol (PI) 3-kinase enzymes with members found in a wide range of intracellular pathogens, including Rickettsia and Legionella spp...
July 24, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30057174/a-gut-commensal-produced-metabolite-mediates-colonization-resistance-to-salmonella-infection
#2
Amanda Jacobson, Lilian Lam, Manohary Rajendram, Fiona Tamburini, Jared Honeycutt, Trung Pham, Will Van Treuren, Kali Pruss, Stephen Russell Stabler, Kyler Lugo, Donna M Bouley, Jose G Vilches-Moure, Mark Smith, Justin L Sonnenburg, Ami S Bhatt, Kerwyn Casey Huang, Denise Monack
The intestinal microbiota provides colonization resistance against pathogens, limiting pathogen expansion and transmission. These microbiota-mediated mechanisms were previously identified by observing loss of colonization resistance after antibiotic treatment or dietary changes, which severely disrupt microbiota communities. We identify a microbiota-mediated mechanism of colonization resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) by comparing high-complexity commensal communities with different levels of colonization resistance...
July 20, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30057172/peroxisome-proliferator-activated-receptor-%C3%AE-is-essential-for-the-resolution-of-staphylococcus-aureus-skin-infections
#3
Lance R Thurlow, Gauri S Joshi, Anthony R Richardson
Skin/soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) represent serious healthcare burdens worldwide. The host initially controls these infections with a pro-inflammatory infiltrate. However, once established, MRSA viability remains constant. To clear established MRSA SSTIs, the host must transition into the post-inflammatory resolution phase marked by infiltration of alternatively activated macrophages. Here we show that the host nuclear receptor, peroxisome proliferation activator receptor γ (PPARγ), is essential for this transition and MRSA clearance...
July 20, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092202/an-atlas-of-genetic-variation-linking-pathogen-induced-cellular-traits-to-human-disease
#4
Liuyang Wang, Kelly J Pittman, Jeffrey R Barker, Raul E Salinas, Ian B Stanaway, Graham D Williams, Robert J Carroll, Tom Balmat, Andy Ingham, Anusha M Gopalakrishnan, Kyle D Gibbs, Alejandro L Antonia, Joseph Heitman, Soo Chan Lee, Gail P Jarvik, Joshua C Denny, Stacy M Horner, Mark R DeLong, Raphael H Valdivia, David R Crosslin, Dennis C Ko
Pathogens have been a strong driving force for natural selection. Therefore, understanding how human genetic differences impact infection-related cellular traits can mechanistically link genetic variation to disease susceptibility. Here we report the Hi-HOST Phenome Project (H2P2): a catalog of cellular genome-wide association studies (GWAS) comprising 79 infection-related phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance for infection-associated phenotypes ranging from pathogen replication to cytokine production...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092201/light-hvem-signaling-in-innate-lymphoid-cell-subsets-protects-against-enteric-bacterial-infection
#5
Goo-Young Seo, Jr-Wen Shui, Daisuke Takahashi, Christina Song, Qingyang Wang, Kenneth Kim, Zbigniew Mikulski, Shilpi Chandra, Daniel A Giles, Sonja Zahner, Pyeung-Hyeun Kim, Hilde Cheroutre, Marco Colonna, Mitchell Kronenberg
Innate lymphoid cells (ILCs) are important regulators of early infection at mucosal barriers. ILCs are divided into three groups based on expression profiles, and are activated by cytokines and neuropeptides. Yet, it remains unknown if ILCs integrate other signals in providing protection. We show that signaling through herpes virus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor superfamily, in ILC3 is important for host defense against oral infection with the bacterial pathogen Yersinia enterocolitica...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092200/species-specific-deamidation-of-cgas-by-herpes-simplex-virus-ul37-protein-facilitates-viral-replication
#6
Junjie Zhang, Jun Zhao, Simin Xu, Junhua Li, Shanping He, Yi Zeng, Linshen Xie, Na Xie, Ting Liu, Katie Lee, Gil Ju Seo, Lin Chen, Alex C Stabell, Zanxian Xia, Sara L Sawyer, Jae Jung, Canhua Huang, Pinghui Feng
Herpes simplex virus 1 (HSV-1) establishes infections in humans and mice, but some non-human primates exhibit resistance via unknown mechanisms. Innate immune recognition pathways are highly conserved but are pivotal in determining susceptibility to DNA virus infections. We report that variation of a single amino acid residue in the innate immune sensor cGAS determines species-specific inactivation by HSV-1. The HSV-1 UL37 tegument protein deamidates human and mouse cGAS. Deamidation impairs the ability of cGAS to catalyze cGAMP synthesis, which activates innate immunity...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092199/a-role-for-fc-function-in-therapeutic-monoclonal-antibody-mediated-protection-against-ebola-virus
#7
Bronwyn M Gunn, Wen-Han Yu, Marcus M Karim, Jennifer M Brannan, Andrew S Herbert, Anna Z Wec, Peter J Halfmann, Marnie L Fusco, Sharon L Schendel, Karthik Gangavarapu, Tyler Krause, Xiangguo Qiu, Shinhua He, Jishnu Das, Todd J Suscovich, Jonathan Lai, Kartik Chandran, Larry Zeitlin, James E Crowe, Douglas Lauffenburger, Yoshihiro Kawaoka, Gary P Kobinger, Kristian G Andersen, John M Dye, Erica Ollmann Saphire, Galit Alter
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092198/vesicle-cloaked-virus-clusters-are-optimal-units-for-inter-organismal-viral-transmission
#8
Marianita Santiana, Sourish Ghosh, Brian A Ho, Vignesh Rajasekaran, Wen-Li Du, Yael Mutsafi, Dennise A De Jésus-Diaz, Stanislav V Sosnovtsev, Eric A Levenson, Gabriel I Parra, Peter M Takvorian, Ann Cali, Christopher Bleck, Anastasia N Vlasova, Linda J Saif, John T Patton, Patrizia Lopalco, Angela Corcelli, Kim Y Green, Nihal Altan-Bonnet
In enteric viral infections, such as those with rotavirus and norovirus, individual viral particles shed in stool are considered the optimal units of fecal-oral transmission. We reveal that rotaviruses and noroviruses are also shed in stool as viral clusters enclosed within vesicles that deliver a high inoculum to the receiving host. Cultured cells non-lytically release rotaviruses and noroviruses inside extracellular vesicles. In addition, stools of infected hosts contain norovirus and rotavirus within vesicles of exosomal or plasma membrane origin...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092197/effect-of-antibiotic-mediated-microbiome-modulation-on-rotavirus-vaccine-immunogenicity-a-human-randomized-control-proof-of-concept-trial
#9
Vanessa C Harris, Bastiaan W Haak, Scott A Handley, Baoming Jiang, Daniel E Velasquez, Barry L Hykes, Lindsay Droit, Guy A M Berbers, Elles Marleen Kemper, Ester M M van Leeuwen, Michael Boele van Hensbroek, Willem Joost Wiersinga
Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092196/enhancing-rotavirus-vaccination-a-microbial-fix
#10
Edward P K Parker, Nicholas C Grassly
Oral rotavirus vaccines have consistently underperformed in low-income countries. In this issue of Cell Host & Microbe,Harris et al. (2018b) explore whether vaccine response can be enhanced via antibiotic-mediated modification of the bacterial microbiota.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092195/engineered-bacteria-for-cholera-prophylaxis
#11
Karla J F Satchell
Over 1.3 billion persons are at risk for cholera globally. Vaccination campaigns are growing, but intervention options providing nearly immediate protection are also needed. Two recent papers in Science Translational Medicine describe probiotic bacteria that reduce intestinal colonization in animal models and show promise for development as prophylaxis agents.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092194/bacterial-prison-break-a-host-protein-mimic-paves-the-way
#12
Siddharth Jaggavarapu, David S Weiss
The intracellular pathogen Francisella secretes effector proteins inside host cells; however, their functions have remained unclear. In this issue of Cell Host & Microbe, Ledvina et al. (2018) elucidate the role of one such effector, OpiA, to be a bacterial phosphatidylinositol-3-kinase that alters phagosomal trafficking and can promote intracellular bacterial replication.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092193/hvem-lights-the-way-for-ilc3s
#13
Daniel Sorobetea, Igor E Brodsky
The early response to bacterial infection requires cytokine responses by immune cells. In this issue of Cell Host & Microbe, Seo et al. (2018) demonstrate that TNF-TNFR superfamily molecules LIGHT and HVEM stimulate early IFN-γ production by type 3 innate lymphoid cells, which are critical for defense against Yersinia enterocolitica.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092192/strength-through-organization-classifying-antibody-activity-against-ebov
#14
M Anthony Moody
In this issue of Cell Host & Microbe and in a related Cell paper, works by Gunn et al. (2018) and Saphire et al. (2018) describe a large number of monoclonal antibodies against Ebola virus (EBOV) and correlate their activity with in vivo protection.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092191/all-aboard-enteric-viruses-travel-together
#15
Carmen Mirabelli, Christiane E Wobus
Individual virus particles have long been accepted as the infectious unit during cellular infection and host-to-host transmission. In this issue of Cell Host & Microbe, Santiana et al. (2018) uncover vesicle-cloaked rotavirus and norovirus clusters in feces of infected hosts that are more infectious than free virus particles during fecal-oral transmission.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30092190/viperin-poisons-viral-replication
#16
Lisa F P Ng, Julian A Hiscox
Control of virus infection relies on the stimulation of interferon-stimulated genes (ISGs) that inhibit viral replication. In a recent Nature paper, Gizzi et al. (2018) discovered that the ISG viperin inhibits virus replication by generating the ribonucleotide ddhCTP, which interferes with RNA synthesis, thus offering insights into drug design.
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30033122/%C3%AE-toxin-induces-platelet-aggregation-and-liver-injury-during-staphylococcus-aureus-sepsis
#17
Bas G J Surewaard, Ajitha Thanabalasuriar, Zhutian Zeng, Christine Tkaczyk, Taylor S Cohen, Bart W Bardoel, Selina K Jorch, Carsten Deppermann, Juliane Bubeck Wardenburg, Rachelle P Davis, Craig N Jenne, Kendall C Stover, Bret R Sellman, Paul Kubes
During sepsis, small blood vessels can become occluded by large platelet aggregates of poorly understood etiology. During Staphylococcal aureus infection, sepsis severity is linked to the bacterial α-toxin (α-hemolysin, AT) through unclear mechanisms. In this study, we visualized intravascular events in the microcirculation and found that intravenous AT injection induces rapid platelet aggregation, forming dynamic micro-thrombi in the microcirculation. These aggregates are retained in the liver sinusoids and kidney glomeruli, causing multi-organ dysfunction...
August 8, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30008293/toxoplasma-parasite-twisting-motion-mechanically-induces-host-cell-membrane-fission-to-complete-invasion-within-a-protective-vacuole
#18
Georgios Pavlou, Mateusz Biesaga, Bastien Touquet, Vanessa Lagal, Martial Balland, Alexandre Dufour, Mohamed-Ali Hakimi, Isabelle Tardieux
To invade cells, the parasite Toxoplasma gondii injects a multi-unit nanodevice into the target cell plasma membrane (PM). The core nanodevice, which is composed of the RhOptry Neck (RON) protein complex, connects Toxoplasma and host cell through a circular tight junction (TJ). We now report that this RON nanodevice mechanically promotes membrane scission at the TJ-PM interface, directing a physical rotation driven by the parasite twisting motion that enables the budding parasitophorous vacuole (PV) to seal and separate from the host cell PM as a bona fide subcellular Toxoplasma-loaded PV...
July 11, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30008292/the-stringent-response-determines-the-ability-of-a-commensal-bacterium-to-survive-starvation-and-to-persist-in-the-gut
#19
Whitman B Schofield, Maria Zimmermann-Kogadeeva, Michael Zimmermann, Natasha A Barry, Andrew L Goodman
In the mammalian gut, bacteria compete for resources to maintain their populations, but the factors determining their success are poorly understood. We report that the human gut bacterium Bacteroides thetaiotaomicron relies on the stringent response, an intracellular signaling pathway that allocates resources away from growth, to survive carbon starvation and persist in the gut. Genome-scale transcriptomics, 13 C-labeling, and metabolomics analyses reveal that B. thetaiotaomicron uses the alarmone (p)ppGpp to repress multiple biosynthetic pathways and upregulate tricarboxylic acid (TCA) cycle genes in these conditions...
July 11, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30008291/zika-virus-vaccine-progress-and-challenges
#20
REVIEW
Chao Shan, Xuping Xie, Pei-Yong Shi
The explosive emergence of Zika virus has inspired a global effort to develop vaccines. Zika virus, which is a flavivirus primarily transmitted by mosquitoes, can cause devastating congenital syndrome in fetuses of pregnant women, including microcephaly, craniofacial disproportion, spasticity, ocular abnormalities, and miscarriage. In adults, Zika infection has been linked to the autoimmune disorder Guillain-Barré syndrome. Thus, despite the current waning in newly reported Zika infections, an efficacious vaccine is urgently needed to help limit the emergence of another detrimental epidemic...
July 11, 2018: Cell Host & Microbe
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