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PLoS Pathogens

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https://www.readbyqxmd.com/read/28806784/structural-analysis-of-p-falciparum-kahrp-and-pfemp1-complexes-with-host-erythrocyte-spectrin-suggests-a-model-for-cytoadherent-knob-protrusions
#1
Erin E Cutts, Niklas Laasch, Dirk M Reiter, Raphael Trenker, Leanne M Slater, Phillip J Stansfeld, Ioannis Vakonakis
Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich Protein (KAHRP) are directly linked to malaria pathology. PfEMP1 and KAHRP cluster on protrusions (knobs) on the P. falciparum-infected erythrocyte surface and enable pathogenic cytoadherence of infected erythrocytes to the host microvasculature, leading to restricted blood flow, oxygen deprivation and damage of tissues. Here we characterize the interactions of PfEMP1 and KAHRP with host erythrocyte spectrin using biophysical, structural and computational approaches...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806780/the-arac-negative-regulator-family-modulates-the-activity-of-histone-like-proteins-in-pathogenic-bacteria
#2
Araceli E Santiago, Michael B Yan, Tracy H Hazen, Brooke Sauder, Mario Meza-Segura, David A Rasko, Melissa M Kendall, Fernando Ruiz-Perez, James P Nataro
The AraC Negative Regulators (ANR) comprise a large family of virulence regulators distributed among diverse clinically important Gram-negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., and pathogenic E. coli strains. We have previously reported broad effects of the ANR members on regulators of the AraC/XylS family. Here, we interrogate possible broader effects of the ANR members on the bacterial transcriptome. Our studies focused on Aar (AggR-activated regulator), an ANR family archetype in enteroaggregative E...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806750/characterization-of-novel-bangle-lectin-from-photorhabdus-asymbiotica-with-dual-sugar-binding-specificity-and-its-effect-on-host-immunity
#3
Gita Jančaříková, Josef Houser, Pavel Dobeš, Gabriel Demo, Pavel Hyršl, Michaela Wimmerová
Photorhabdus asymbiotica is one of the three recognized species of the Photorhabdus genus, which consists of gram-negative bioluminescent bacteria belonging to the family Morganellaceae. These bacteria live in a symbiotic relationship with nematodes from the genus Heterorhabditis, together forming a complex that is highly pathogenic for insects. Unlike other Photorhabdus species, which are strictly entomopathogenic, P. asymbiotica is unique in its ability to act as an emerging human pathogen. Analysis of the P...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#4
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800624/destabilizing-polymorphism-in-cervid-prion-protein-hydrophobic-core-determines-prion-conformation-and-conversion-efficiency
#5
Samia Hannaoui, Sara Amidian, Yo Ching Cheng, Camilo Duque Velásquez, Lyudmyla Dorosh, Sampson Law, Glenn Telling, Maria Stepanova, Debbie McKenzie, Holger Wille, Sabine Gilch
Prion diseases are infectious neurodegenerative disorders of humans and animals caused by misfolded forms of the cellular prion protein PrPC. Prions cause disease by converting PrPC into aggregation-prone PrPSc. Chronic wasting disease (CWD) is the most contagious prion disease with substantial lateral transmission, affecting free-ranging and farmed cervids. Although the PrP primary structure is highly conserved among cervids, the disease phenotype can be modulated by species-specific polymorphisms in the prion protein gene...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#6
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800584/expression-of-the-rna-binding-protein-rbp10-promotes-the-bloodstream-form-differentiation-state-in-trypanosoma-brucei
#7
Elisha Mugo, Christine Clayton
In nearly all eukaryotes, cellular differentiation is governed by changes in transcription, and stabilized by chromatin and DNA modification. Gene expression control in the pathogen Trypanosoma brucei, in contrast, relies almost exclusively on post-transcriptional mechanisms, so RNA binding proteins must assume the burden that is usually borne by transcription factors. T. brucei multiply in the blood of mammals as bloodstream forms, and in the midgut of Tsetse flies as procyclic forms. We show here that a single RNA-binding protein, RBP10, promotes the bloodstream-form trypanosome differentiation state...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28797122/cross-seeding-of-prions-by-aggregated-%C3%AE-synuclein-leads-to-transmissible-spongiform-encephalopathy
#8
Elizaveta Katorcha, Natallia Makarava, Young Jin Lee, Iris Lindberg, Mervyn J Monteiro, Gabor G Kovacs, Ilia V Baskakov
Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, prion and other diseases. Recent years have witnessed a growing number of reports of overlap in neuropathological features that were once thought to be unique to only one neurodegenerative disorder. However, the origin for the overlap remains unclear. One possibility is that diseases with mixed brain pathologies might arise from cross-seeding of one amyloidogenic protein by aggregated states of unrelated proteins...
August 10, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28793349/ligation-of-dectin-2-with-a-novel-microbial-ligand-promotes-adjuvant-activity-for-vaccination
#9
Huafeng Wang, Taek-Jin Lee, Scott J Fites, Richard Merkhofer, Robert Zarnowski, Tristan Brandhorst, Kevin Galles, Bruce Klein, Marcel Wüthrich
The development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants. While most current vaccines against infectious diseases preferentially induce production of antibodies, cellular immunity is essential for the resolution of fungal infections. Microbes such as fungi and Mycobacterium tuberculosis require Th17 and Th1 cells for resistance, and engage the C-type lectin receptors including Dectin-2. Herein, we discovered a novel Dectin-2 ligand, the glycoprotein Blastomyces Eng2 (Bl-Eng2)...
August 9, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28787457/acquisition-of-rab11-and-rab11-fip2-a-novel-strategy-for-chlamydia-pneumoniae-early-survival
#10
Katja Mölleken, Johannes H Hegemann
The initial steps in chlamydial infection involve adhesion and internalization into host cells and, most importantly, modification of the nascent inclusion to establish the intracellular niche. Here, we show that Chlamydia pneumoniae enters host cells via EGFR-dependent endocytosis into an early endosome with a phosphatidylinositol 3-phosphate (PI3P) membrane identity. Immediately after entry, the early chlamydial inclusion acquires early endosomal Rab GTPases including Rab4, Rab5, Rab7, as well as the two recycling-specific Rabs Rab11 and Rab14...
August 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28787456/a-parapoxviral-virion-protein-inhibits-nf-%C3%AE%C2%BAb-signaling-early-in-infection
#11
Sushil Khatiwada, Gustavo Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G Diel, Eduardo F Flores, Daniel L Rock
Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection)...
August 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28787455/hiv-1-epitopes-presented-by-mhc-class-i-types-associated-with-superior-immune-containment-of-viremia-have-highly-constrained-fitness-landscapes
#12
Aleksandr M Gorin, Yushen Du, Franklin Y Liu, Tian-Hao Zhang, Hwee L Ng, Christian Hofmann, William G Cumberland, Ren Sun, Otto O Yang
Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing...
August 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28787450/infection-adapted-emergency-hematopoiesis-promotes-visceral-leishmaniasis
#13
Belma Melda Abidin, Akil Hammami, Simona Stäger, Krista M Heinonen
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 differentiation on the persistence of chronic infections is poorly understood. We have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype...
August 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28787449/a-siv-molecular-clone-that-targets-the-cns-and-induces-neuroaids-in-rhesus-macaques
#14
Kenta Matsuda, Nadeene E Riddick, Cheri A Lee, Sarah B Puryear, Fan Wu, Bernard A P Lafont, Sonya Whitted, Vanessa M Hirsch
Despite effective control of plasma viremia with the use of combination antiretroviral therapies (cART), minor cognitive and motor disorders (MCMD) persist as a significant clinical problem in HIV-infected patients. Non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (CNS). We isolated a strain of simian immunodeficiency virus (SIV), SIVsm804E, which induces neuroAIDS in a high proportion of rhesus macaques and identified enhanced antagonism of the host innate factor BST-2 as an important factor in the macrophage tropism and initial neuro-invasion of this isolate...
August 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28771621/pseudomonas-aeruginosa-exou-augments-neutrophil-transepithelial-migration
#15
Michael A Pazos, Bernard B Lanter, Lael M Yonker, Alex D Eaton, Waheed Pirzai, Karsten Gronert, Joseph V Bonventre, Bryan P Hurley
Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa...
August 3, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28771584/extracellular-motility-and-cell-to-cell-transmission-of-enterohemorrhagic-e-coli-is-driven-by-espfu-mediated-actin-assembly
#16
Katrina B Velle, Kenneth G Campellone
Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are closely-related pathogens that attach tightly to intestinal epithelial cells, efface microvilli, and promote cytoskeletal rearrangements into protrusions called actin pedestals. To trigger pedestal formation, EPEC employs the tyrosine phosphorylated transmembrane receptor Tir, while EHEC relies on the multivalent scaffolding protein EspFU. The ability to generate these structures correlates with bacterial colonization in several animal models, but the precise function of pedestals in infection remains unclear...
August 3, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28759611/tpl-2-restricts-ccl24-dependent-immunity-to-heligmosomoides-polygyrus
#17
Yashaswini Kannan, Lewis J Entwistle, Victoria S Pelly, Jimena Perez-Lloret, Alan W Walker, Steven C Ley, Mark S Wilson
TPL-2 (COT, MAP3K8) kinase activates the MEK1/2-ERK1/2 MAPK signaling pathway in innate immune responses following TLR, TNFR1 and IL-1R stimulation. TPL-2 contributes to type-1/Th17-mediated autoimmunity and control of intracellular pathogens. We recently demonstrated TPL-2 reduces severe airway allergy to house dust mite by negatively regulating type-2 responses. In the present study, we found that TPL-2 deficiency resulted in resistance to Heligmosomoides polygyrus infection, with accelerated worm expulsion, reduced fecal egg burden and reduced worm fitness...
July 31, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28704543/the-transcriptional-regulator-ssrb-is-involved-in-a-molecular-switch-controlling-virulence-lifestyles-of-salmonella
#18
Deyanira Pérez-Morales, María M Banda, N Y Elizabeth Chau, Heladia Salgado, Irma Martínez-Flores, J Antonio Ibarra, Bushra Ilyas, Brian K Coombes, Víctor H Bustamante
The evolution of bacterial pathogenicity, heavily influenced by horizontal gene transfer, provides new virulence factors and regulatory connections that alter bacterial phenotypes. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) are chromosomal regions that were acquired at different evolutionary times and are essential for Salmonella virulence. In the intestine of mammalian hosts, Salmonella expresses the SPI-1 genes that mediate its invasion to the gut epithelium. Once inside the cells, Salmonella down-regulates the SPI-1 genes and induces the expression of the SPI-2 genes, which favor its intracellular replication...
July 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806402/multi-functional-mechanisms-of-immune-evasion-by-the-streptococcal-complement-inhibitor-c5a-peptidase
#19
Nicola N Lynskey, Mark Reglinski, Damien Calay, Matthew K Siggins, Justin C Mason, Marina Botto, Shiranee Sriskandan
The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28796840/yes-research-matters
#20
Mari L Shinohara
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 his case, the diagnosis started from a suggestion by his doctor to check whether he had a gastric infection with Helicobacter pylori, a bacterial species found in the digestive tract. In Japan, where he lives, a majority of gastric cancer patients (more than 99%) have been infected with H...
August 2017: PLoS Pathogens
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