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Cellular Microbiology

Michael Dominic Chua, Ci-Hong Liou, Alexander Constantine Bogdan, Hong T Law, Kuo-Ming Yeh, Jung-Chung Lin, L Kristopher Siu, Julian Andrew Guttman
Klebsiella pneumoniae raises significant concerns to the health care industry as these microbes are the source of widespread contamination of medical equipment, cause pneumonia as well as other multi-organ metastatic infections and have gained multi-drug resistance. Despite soaring mortality rates, the host cell alterations occurring during these infections remain poorly understood. Here, we show that during in vitro and in vivo K. pneumoniae infections of lung epithelia, microtubules are severed and then eliminated...
November 11, 2018: Cellular Microbiology
Ryota Otsubo, Hitomi Mimuro, Hiroshi Ashida, Jun Hamazaki, Shigeo Murata, Chihiro Sasakawa
Subversion of antigen-specific immune responses by intracellular pathogens is pivotal for successful colonization. Bacterial pathogens, including Shigella, deliver effectors into host cells via the type III secretion system (T3SS) in order to manipulate host innate and adaptive immune responses, thereby promoting infection. However, the strategy for subverting antigen-specific immunity is not well understood. Here, we show that Shigella flexneri invasion plasmid antigen H (IpaH) 4.5, a member of the E3 ubiquitin ligase effector family, targets the proteasome regulatory particle non-ATPase 13 (RPN13) and induces its degradation via the ubiquitin-proteasome system (UPS)...
November 10, 2018: Cellular Microbiology
Yuanyuan Li, Ying Shen, Dandan Lin, Hongbo Zhang, Ting Wang, Haiyan Liu, Yiqiang Wang
Bacterial flagellar hook and recombinant flagellar hook protein E (FlgE) were reportedly immunostimulatory in mammalian cells or tissues. Current study focused on the mechanisms underlying FlgE stimulation. In an acute lung injury (ALI) model induced by intranasal FlgE challenge, neutrophils were the predominant infiltrates in lungs, and depletion of neutrophils with anti-Ly6G antibody attenuated FlgE-induced lung damage. However, the FlgE-induced neutrophils recruitment, neutrophils reactive oxygen species (ROS) generation, as well as neutrophil extracellular trap (NETs) formation were significantly impaired in Il17a-/- mice compared with those in wild type (WT) mice...
November 9, 2018: Cellular Microbiology
Perle Latré De Laté, Malak Haidar, Hifzur Ansari, Shahin Tajeri, Eszter Szarka, Anita Alexa, Kerry Woods, Attila Reményi, Arnab Pain, Gordon Langsley
Constitutive JNK activity characterizes bovine T and B cells infected with Theileria parva, and B cells and macrophages infected with T. annulata. Here, we show that T. annulata infection of macrophages manipulates JNK activation by recruiting JNK2 and not JNK1 to the parasite surface, whereas JNK1 is found predominantly in the host cell nucleus. At the parasite's surface JNK2 forms a complex with p104 a GPI-anchored T. annulata plasma membrane protein. Sequestration of JNK2 depended on PKA-mediated phosphorylation of a JNK-binding motif common to T...
November 9, 2018: Cellular Microbiology
Victoria Gillan, Deborah M Simpson, Jane Kinnaird, Kirsty Maitland, Brian Shiels, Eileen Devaney
The protozoan parasites, Theileria annulata and T. parva are unique amongst intracellular eukaryotic pathogens as they induce a transformation-like phenotype in their bovine host cell. T. annulata causes tropical theileriosis, which is frequently fatal, with infected leukocytes becoming metastatic and forming foci in multiple organs resulting in destruction of the lymphoid system. Exosomes, a sub-set of extracellular vesicles (EV), are critical in metastatic progression in many cancers. Here we characterised the cargo of EV from a control bovine lymphosarcoma cell line (BL20) and BL20 infected with T...
October 29, 2018: Cellular Microbiology
Ashley M Best, Yousef Abu Kwaik
Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes...
October 29, 2018: Cellular Microbiology
Anthony Mannion, Zeli Shen, Yan Feng, Stephen C Artim, Kodihalli Ravindra, Zhongming Ge, James G Fox
BACKGROUND: Helicobacter saguini is a novel enterohepatic Helicobacter species isolated from captive cotton top tamarins with chronic colitis and colon cancer. Mono-associated H. saguini infection in gnotobiotic IL-10-/- mice causes typhlocolitis and dysplasia; however, the virulent mechanisms of this species are unknown. Gamma-glutamyltranspeptidase (GGT) is an enzymatic virulence factor expressed by pathogenic Helicobacter and Campylobacter species that inhibits host cellular proliferation and promotes inflammatory-mediated gastrointestinal pathology...
October 26, 2018: Cellular Microbiology
Yong Fu, Xia Cui, Jing Liu, Xiao Zhang, Heng Zhang, Congshan Yang, Qun Liu
Toxoplasma gondii relies on apicoplast-localized FASII pathway and endoplasmic reticulum-associated fatty acid elongation pathway for the synthesis of fatty acids, which flow through lipid metabolism mainly in the form of long-chain acyl-CoA (LCACoAs) esters. Functions of Toxoplasma acyl-CoA transporters in lipid metabolism remain unclear. Here, we investigated the roles of acyl-CoA-binding protein (TgACBP1) and a sterol carrier protein-2 (TgSCP2) as cytosolic acyl-CoA transporters in lipid metabolism. The fluormetric binding assay and yeast complementation confirmed the acyl-CoA binding activities of TgACBP1 and TgSCP2, respectively...
October 26, 2018: Cellular Microbiology
Patrik Nygren, Nataliya Balashova, Angela C Brown, Irene Kieba, Anuradha Dhingra, Kathleen Boesze-Battaglia, Edward T Lally
Repeats-in-toxin (RTX) leukotoxin LtxA produced by the oral bacterium Aggregatibacter actinomycetemcomitans kills human leukocytes in a lymphocyte function-associated antigen-1 (LFA-1, integrin αL /β2 )-dependent manner, although the mechanism for this interaction has not been identified. LtxA internalization by LFA-1- expressing cells was explored with FRET microscopy using a cell line that expresses LFA-1 with a CFP-tagged cytosolic αL domain and an YFP-tagged β2 domain. Phorbol 12-myristate 13-acetate (PMA) activation of LFA-1 caused transient cytosolic domain separation...
October 17, 2018: Cellular Microbiology
Alexia Dumas, Lucie Bernard, Yannick Poquet, Geanncarlo Lugo-Villarino, Olivier Neyrolles
The pulmonary microbial community, described only a few years ago, forms a discreet part of the human host microbiota. The airway microbiota has been found to be substantially altered in the context of numerous respiratory disorders; nonetheless, its role in health and disease is as yet only poorly understood. Another important parameter to consider is the gut-lung axis, where distal (gut) immune modulation during respiratory disease is mediated by the gut microbiota. The use of specific microbiota strains, termed "probiotics," with beneficial effects on the host immunity and/or against pathogens, has proven successful in the treatment of intestinal disorders and is also showing promise in the context of airway diseases...
October 17, 2018: Cellular Microbiology
Allon Weiner, François Orange, Sandra Lacas-Gervais, Katya Rechav, Vikram Ghugtyal, Martine Bassilana, Robert A Arkowitz
Candida albicans is an opportunistic fungal pathogen that colonizes the skin as well as genital and intestinal mucosa of most healthy individuals. The ability of C. albicans to switch between different morphological states, e.g. from an ellipsoid yeast form to a highly polarized, hyphal form, contributes to its success as a pathogen. In highly polarized tip growing cells such as neurons, pollen tubes and filamentous fungi, delivery of membrane and cargo to the filament apex is achieved by long-range delivery of secretory vesicles tethered to motors moving along cytoskeletal cables that extend towards the growing tip...
October 15, 2018: Cellular Microbiology
Nicole Tegtmeyer, Aileen Harrer, Verena Schmitt, Bernhard B Singer, Steffen Backert
Helicobacter pylori represents an important pathogen involved in diseases ranging from gastritis, peptic ulceration to gastric malignancies. Prominent virulence factors comprise the vacuolating cytotoxin VacA and the cytotoxin-associated genes pathogenicity island (cagPAI) encoded type-IV secretion system (T4SS). The T4SS effector protein CagA can be translocated into AGS and other gastric epithelial cells followed by phosphorylation through c-Src and c-Abl tyrosine kinases to hijack signaling networks. The duodenal cell line AZ-521 has been recently introduced as novel model system to investigate CagA delivery and phosphorylation in a VacA-dependent fashion...
October 15, 2018: Cellular Microbiology
Yusuke Kurihara, Ryota Itoh, Akinori Shimizu, Nirwana Fitriani Walenna, Bin Chou, Kazunari Ishii, Toshinori Soejima, Aya Fujikane, Kenji Hiromatsu
Chlamydia trachomatis is an obligate intracellular bacterium that scavenges host metabolic products for its replication. Mitochondria are the power plants of eukaryotic cells and provide most of the cellular ATP via oxidative phosphorylation. Several intracellular pathogens target mitochondria as part of their obligatory cellular reprogramming. This study was designed to analyse the mitochondrial morphological changes in response to C. trachomatis infection in HeLa cells. Mitochondrial elongation and fragmentation were found at the early stages and late stages of C...
October 12, 2018: Cellular Microbiology
Tomoko Ishino, Eri Murata, Naohito Tokunaga, Minami Baba, Mayumi Tachibana, Amporn Thongkukiatkul, Takafumi Tsuboi, Motomi Torii
Malaria parasite transmission to humans is initiated by the inoculation of Plasmodium sporozoites into the skin by mosquitoes. Sporozoites develop within mosquito midgut oocysts, first invade the salivary glands of mosquitoes, and finally infect hepatocytes in mammals. The apical structure of sporozoites is conserved with the infective forms of other apicomplexan parasites that have secretory organelles, such as rhoptries and micronemes. Because some rhoptry proteins are crucial for Plasmodium merozoite infection of erythrocytes, we examined the roles of rhoptry proteins in sporozoites...
October 11, 2018: Cellular Microbiology
Gaurav Bairwa, Mélissa Caza, Linda Horianopoulos, Guanggan Hu, James Kronstad
Heme is a major source of iron for pathogens of humans, and its use is critical in determining the outcome of infection and disease. Cryptococcus neoformans is an encapsulated fungal pathogen that causes life-threatening infections in immunocompromised individuals. C. neoformans effectively uses heme as an iron source but the underlying mechanisms are poorly defined. Non-iron metalloporphyrins (MPPs) are toxic analogues of heme and are thought to enter microbial cells via endogenous heme acquisition systems...
October 6, 2018: Cellular Microbiology
Rongbo Che, Shibiao Ding, Qinchao Zhang, Weiqun Yang, Jie Yan, Xu'ai Lin
Leptospira interrogans causes widespread leptospirosis in humans and animals, with major symptoms of jaundice and hemorrhage. Sph2, a member of the sphingomyelinase hemolysins, is an important virulence factor for leptospire. In this study, the function and mechanism of Sph2 in the pathogenesis of leptospirosis were investigated to further understand the pathogenesis of leptospire. Real-time PCR analysis of expression levels during cell invasion showed that sph2 gene expression was transiently induced in human umbilical vein endothelial cells (HUVEC), human embryo liver cells (L02) and human epithelial lung cells (L132), with expression levels reaching a peak after 45 min of infection...
October 2, 2018: Cellular Microbiology
Pratik P Vikhe, Tom Purnell, Steve D M Brown, Derek W Hood
Non-typeable Haemophilus influenzae (NTHi) is a major pathogen causing acute otitis media (AOM). The relationship between the cellular content of the middle ear fluid (MEF) during AOM and infection of NTHi is poorly understood. Using the Junbo mouse, a characterised NTHi infection model, we analysed the cellular content of MEF and correlated the data with NTHi titres. The MEF of the Junbo mouse was heterogeneous between ears and was graded from 1 to 5; 1 being highly serous/clear and 5 being heavily viscous/opaque...
September 28, 2018: Cellular Microbiology
Kristine von Bargen, Mirella Scraba, Ina Krämer, Maren Ketterer, Christian Nehls, Sina Krokowski, Urska Repnik, Michaela Wittlich, Anna Maaser, Pia Zapka, Madeleine Bunge, Martin Schlesinger, Gitta Huth, Annette Klees, Philipp Hansen, Andreas Jeschke, Gerd Bendas, Olaf Utermöhlen, Gareth Griffiths, Thomas Gutsmann, Jens Wohlmann, Albert Haas
Professional phagocytic cells such as macrophages are a central part of innate immune defense. They ingest microorganisms into membrane-bound compartments (phagosomes) which acidify and eventually fuse with lysosomes, exposing their contents to a microbicidal environment. Gram-positive Rhodococcus equi can cause pneumonia in young foals and in immunocompromised humans. The possession of a virulence plasmid allows them to subvert host defence mechanisms and to multiply in macrophages. Here we show that the plasmid-encoded and secreted Virulence-associated protein A (VapA) participates in exclusion of the proton-pumping vacuolar-ATPase complex from phagosomes and causes membrane permeabilization, thus contributing to a pH-neutral phagosome lumen...
September 24, 2018: Cellular Microbiology
Anuradha Vajjala, Debabrata Biswas, Wei Hong Tay, Emanuel Hanski, Kimberly A Kline
Group A Streptococcus (GAS) is a human pathogen that causes infections ranging from mild to fulminant and life-threatening. Biofilms have been implicated in acute GAS soft-tissue infections such as necrotising fasciitis (NF). However, most in vitro models used to study GAS biofilms have been designed to mimic chronic infections and insufficiently recapitulate in vivo conditions along with the host-pathogen interactions that might influence biofilm formation. Here, we establish and characterise an in vitro model of GAS biofilm development on mammalian cells that simulates microcolony formation observed in a mouse model of human NF...
September 21, 2018: Cellular Microbiology
Hannah F Preugschas, Eike R Hrincius, Carolin Mewis, Giao V Q Tran, Stephan Ludwig, Christina Ehrhardt
Activation of the Raf/MEK/ERK cascade is required for efficient propagation of several RNA and DNA viruses, including human respiratory syncytial virus (RSV). In RSV infection, activation of the Raf/MEK/ERK cascade is biphasic. An early induction within minutes after infection is associated with viral attachment. Subsequently, a second activation occurs with, so far, unknown function in the viral life cycle. In this study, we aimed to characterise the role of Raf/MEK/ERK-mediated signalling during ongoing RSV infection...
September 17, 2018: Cellular Microbiology
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