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Cell Host & Microbe

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https://www.readbyqxmd.com/read/28494245/global-reprogramming-of-host-kinase-signaling-in-response-to-fungal-infection
#1
Aseem Pandey, Sheng Li Ding, Qing-Ming Qin, Rahul Gupta, Gabriel Gomez, Furong Lin, Xuehuan Feng, Luciana Fachini da Costa, Sankar P Chaki, Madhu Katepalli, Elizabeth D Case, Erin J van Schaik, Tabasum Sidiq, Omar Khalaf, Angela Arenas, Koichi S Kobayashi, James E Samuel, Gonzalo M Rivera, Robert C Alaniz, Sing-Hoi Sze, Xiaoning Qian, William J Brown, Allison Rice-Ficht, William K Russell, Thomas A Ficht, Paul de Figueiredo
Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection. Our analysis reveals numerous and diverse host proteins that are differentially phosphorylated following fungal ingestion by macrophages, thereby indicating global reprogramming of host kinase signaling. Notably, phagocytosis of the pathogen activates the host autophagy initiation complex (AIC) and the upstream regulatory components LKB1 and AMPKα, which regulate autophagy induction through their kinase activities...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494244/quorum-sensing-attenuates-virulence-in-sodalis-praecaptivus
#2
Shinichiro Enomoto, Abhishek Chari, Adam Larsen Clayton, Colin Dale
Sodalis praecaptivus is a close relative and putative environmental progenitor of the widely distributed, insect-associated, Sodalis-allied symbionts. Here we show that mutant strains of S. praecaptivus that lack genetic components of a quorum-sensing (QS) apparatus have a rapid and potent killing phenotype following microinjection into an insect host. Transcriptomic and genetic analyses indicate that insect killing occurs as a consequence of virulence factors, including insecticidal toxins and enzymes that degrade the insect integument, which are normally repressed by QS at high infection densities...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494243/a-rab20-dependent-membrane-trafficking-pathway-controls-m-%C3%A2-tuberculosis-replication-by-regulating-phagosome-spaciousness-and-integrity
#3
Laura Schnettger, Angela Rodgers, Urska Repnik, Rachel P Lai, Gang Pei, Martijn Verdoes, Robert J Wilkinson, Douglas B Young, Maximiliano G Gutierrez
The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494242/pseudomonas-aeruginosa-effector-exos-inhibits-ros-production-in-human-neutrophils
#4
Chairut Vareechon, Stephanie Elizabeth Zmina, Mausita Karmakar, Eric Pearlman, Arne Rietsch
Neutrophils are the first line of defense against bacterial infections, and the generation of reactive oxygen species is a key part of their arsenal. Pathogens use detoxification systems to avoid the bactericidal effects of reactive oxygen species. Here we demonstrate that the Gram-negative pathogen Pseudomonas aeruginosa is susceptible to reactive oxygen species but actively blocks the reactive oxygen species burst using two type III secreted effector proteins, ExoS and ExoT. ExoS ADP-ribosylates Ras and prevents it from interacting with and activating phosphoinositol-3-kinase (PI3K), which is required to stimulate the phagocytic NADPH-oxidase that generates reactive oxygen species...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494241/gut-microbiome-function-predicts-response-to-anti-integrin-biologic-therapy-in-inflammatory-bowel-diseases
#5
Ashwin N Ananthakrishnan, Chengwei Luo, Vijay Yajnik, Hamed Khalili, John J Garber, Betsy W Stevens, Thomas Cleland, Ramnik J Xavier
The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494240/cooperating-commensals-restore-colonization-resistance-to-vancomycin-resistant-enterococcus-faecium
#6
Silvia Caballero, Sohn Kim, Rebecca A Carter, Ingrid M Leiner, Bože Sušac, Liza Miller, Grace J Kim, Lilan Ling, Eric G Pamer
Antibiotic-mediated microbiota destruction and the consequent loss of colonization resistance can result in intestinal domination with vancomycin-resistant Enterococcus (VRE), leading to bloodstream infection in hospitalized patients. Clearance of VRE remains a challenging goal that, if achieved, would reduce systemic VRE infections and patient-to-patient transmission. Although obligate anaerobic commensal bacteria have been associated with colonization resistance to VRE, the specific bacterial species involved remain undefined...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494239/crispr-cas9-screens-reveal-epstein-barr-virus-transformed-b-cell-host-dependency-factors
#7
Yijie Ma, Michael J Walsh, Katharina Bernhardt, Camille W Ashbaugh, Stephen J Trudeau, Isabelle Y Ashbaugh, Sizun Jiang, Chang Jiang, Bo Zhao, David E Root, John G Doench, Benjamin E Gewurz
Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (BL) and immunosuppression-related lymphomas. These B cell malignancies arise by distinct transformation pathways and have divergent viral and host expression programs. To identify host dependency factors resulting from these EBV+, B cell-transformed cell states, we performed parallel genome-wide CRISPR/Cas9 loss-of-function screens in BL and lymphoblastoid cell lines (LCLs). These highlighted 57 BL and 87 LCL genes uniquely important for their growth and survival...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494238/smyd2-mediated-histone-methylation-contributes-to-hiv-1-latency
#8
Daniela Boehm, Mark Jeng, Gregory Camus, Andrea Gramatica, Roland Schwarzer, Jeffrey R Johnson, Philip A Hull, Mauricio Montano, Naoki Sakane, Sara Pagans, Robert Godin, Steven G Deeks, Nevan J Krogan, Warner C Greene, Melanie Ott
Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation, but the underlying mechanisms are incompletely understood. We performed an RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological inhibition reactivated latent HIV-1 in T cell lines and in primary CD4(+) T cells...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494237/microbial-vertical-transmission-during-human-pregnancy
#9
REVIEW
Nitin Arora, Yoel Sadovsky, Terence S Dermody, Carolyn B Coyne
Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity and mortality worldwide. Despite the devastating impact of microbial infections on the developing fetus, relatively little is known about how pathogens associated with congenital disease breach the placental barrier to transit vertically during human pregnancy. In this Review, we focus on transplacental transmission of pathogens during human gestation...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494236/allied-commensal-forces-against-vancomycin-resistant-enterococci
#10
Brayon J Fremin, Ami S Bhatt
In this issue of Cell Host & Microbe, Caballero et al. (2017) define a precise, limited consortium of commensal bacteria that restores resistance to colonization by clinically vexing vancomycin-resistant Enterococcus species.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494235/ade-ing-and-abetting-zika
#11
Jinsheng Wen, Sujan Shresta
Although dengue virus (DENV) antibodies can neutralize or enhance Zika virus (ZIKV) infection in vitro, their contribution to ZIKV infection in vivo remains unclear. In a recent issue of Science, Bardina et al. (2017) explore the protective versus pathogenic roles of DENV-immune antibodies in ZIKV infection using a mouse model.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494234/an-elegan-t-screen-for-drug-microbe-interactions
#12
Alison Vrbanac, Justine W Debelius, Lingjing Jiang, James T Morton, Pieter Dorrestein, Rob Knight
Microbes affect drug responses, but mechanisms remain elusive. Two papers in Cell exploit C. elegans to infer anticancer drug mechanisms. Through high-throughput screens of drug-microbe-host interactions, García-González et al. (2017) and Scott et al. (2017) determine that bacterial metabolism underpins fluoropyrimidine cytotoxicity, providing a paradigm for unraveling bacterial mechanisms in drug metabolism.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494233/don-t-bite-the-hand-that-feeds-you
#13
Rita V M Rio
Eukaryotic-bacterial symbioses are ubiquitous in nature. Pathogens and symbionts employ similar machinery, yet symbionts can minimize host damage. In this issue of Cell Host & Microbe, Enomoto et al. (2017) demonstrate how quorum sensing regulates expression of virulence genes at appropriate times, thereby enabling symbiont retention throughout the host lifespan.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494232/ras-and-ros-a-story-of-pseudomonas-survival
#14
Stacey L Kolar, George Y Liu
Some pathogens block generation of reactive oxygen species to evade neutrophil killing, but how that is accomplished is poorly understood. In this issue of Cell Host & Microbe, Vareechon et al. (2017) describe ADP-ribosylation of Ras as a strategy to inhibit assembly of neutrophil NADPH oxidase.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494231/hiv-latency-gets-a-new-histone-mark
#15
Bryan C Nikolai, Qin Feng
Transcriptional latency of integrated HIV-1 provirus represents a major obstacle to curing HIV. In this issue of Cell Host & Microbe, Boehm et al. (2017) identify a new lysine methyltransferase that writes a repressive histone mark associated with HIV-1 latency. The results are important for strategies to pharmacologically reverse HIV-1 latency.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407488/the-matrix-protein-of-human-parainfluenza-virus-type-3-induces-mitophagy-that-suppresses-interferon-responses
#16
Binbin Ding, Linliang Zhang, Zhifei Li, Yi Zhong, Qiaopeng Tang, Yali Qin, Mingzhou Chen
Mitophagy is a form of autophagy that selectively removes damaged mitochondria. Impaired mitochondria can be tagged by the kinase PINK1, which triggers recruitment of the E3-ubiquitin ligase Parkin and subsequent mitochondrial sequestration within autophagosomes. We previously found that human parainfluenza virus type 3 (HPIV3) infection induces autophagy, but the type and mechanisms of autophagy induction remain unknown. Here, we show that matrix protein (M) of HPIV3 translocates to mitochondria and interacts with Tu translation elongation factor mitochondrial (TUFM)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407487/matching-nlr-immune-receptors-to-autoimmunity-in-camta3-mutants-using-antimorphic-nlr-alleles
#17
Signe Lolle, Christiaan Greeff, Klaus Petersen, Milena Roux, Michael Krogh Jensen, Simon Bressendorff, Eleazar Rodriguez, Kenneth Sømark, John Mundy, Morten Petersen
To establish infection, pathogens deploy effectors to modify or remove host proteins. Plant immune receptors with nucleotide-binding, leucine-rich repeat domains (NLRs) detect these modifications and trigger immunity. Plant NLRs thus guard host "guardees." A corollary is that autoimmunity may result from inappropriate NLR activation because mutations in plant guardees could trigger corresponding NLR guards. To explore these hypotheses, we expressed 108 dominant-negative (DN) Arabidopsis NLRs in various lesion mimic mutants, including camta3, which exhibits autoimmunity...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407486/transcriptional-elongation-of-hsv-immediate-early-genes-by-the-super-elongation-complex-drives-lytic-infection-and-reactivation-from-latency
#18
Roberto Alfonso-Dunn, Anne-Marie W Turner, Pierre M Jean Beltran, Jesse H Arbuckle, Hanna G Budayeva, Ileana M Cristea, Thomas M Kristie
The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the super elongation complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation, and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407485/defective-hiv-1-proviruses-are-expressed-and-can-be-recognized-by-cytotoxic-t-lymphocytes-which-shape-the-proviral-landscape
#19
Ross A Pollack, R Brad Jones, Mihaela Pertea, Katherine M Bruner, Alyssa R Martin, Allison S Thomas, Adam A Capoferri, Subul A Beg, Szu-Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C Yong, Colin Kovacs, Erika Benko, Robert F Siliciano, Ya-Chi Ho
Despite antiretroviral therapy, HIV-1 persists in memory CD4(+) T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407484/autoreactive-t-cells-and-chronic-fungal-infection-drive-esophageal-carcinogenesis
#20
Feng Zhu, Jami Willette-Brown, Na-Young Song, Dakshayani Lomada, Yongmei Song, Liyan Xue, Zane Gray, Zitong Zhao, Sean R Davis, Zhonghe Sun, Peilin Zhang, Xiaolin Wu, Qimin Zhan, Ellen R Richie, Yinling Hu
Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell-driven autoimmune disease caused by impaired central tolerance, are susceptible to chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop APECED-like phenotypes, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers...
April 12, 2017: Cell Host & Microbe
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