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R Pandey, L Chen, C Manca, S Jenkins, L Glaser, C Vinnard, G Stone, J Lee, B Mathema, E L Nuermberger, R A Bonomo, B N Kreiswirth
As a consequence of a growing population of immunocompromised individuals, including transplant recipients and cystic fibrosis patients, there has been a dramatic increase in chronic infections caused by Mycobacterium abscessus complex (MABC) strains that are usually recalcitrant to effective antibiotic therapy. The recent rise of macrolide resistance in MABC has further complicated this clinical dilemma, dramatizing the need for novel agents. The repurposing of current antibiotics is one rapid path from discovery to patient care...
February 12, 2019: MBio
Dongli Pan, Gang Li, Jenna Morris-Love, Shuyuan Qi, Lei Feng, Max E Mertens, Igor Jurak, David M Knipe, Donald M Coen
Herpes simplex virus 1 (HSV-1) switches between two infection programs, productive ("lytic") and latent infection. Some HSV-1 microRNAs (miRNAs) have been hypothesized to help control this switch, and yet little is known about regulation of their expression. Using Northern blot analyses, we found that, despite inherent differences in biogenesis efficiency among six HSV-1 miRNAs, all six exhibited high pre-miRNA/miRNA ratios during lytic infection of different cell lines and, when detectable, in acutely infected mouse trigeminal ganglia...
February 12, 2019: MBio
Oya Cingöz, Stephen P Goff
Effective host immune responses against viral infection rely on the detection of the virus, activation of downstream signaling pathways, and the secretion of interferons (IFNs) and other cytokines. Many viruses can potently stimulate these responses, whereas the immune response against human immunodeficiency virus type 1 (HIV-1) remains relatively less well characterized. Here we show that HIV-1 infection with reporter viruses does not activate sensing pathways in cell lines and primary cells that are otherwise responsive to foreign nucleic acids...
February 12, 2019: MBio
Andrew L Chang, Yiming Kang, Tamara L Doering
Cryptococcus neoformans kills 200,000 people worldwide each year. After inhalation, this environmental yeast proliferates either extracellularly or within host macrophages. Under conditions of immunocompromise, cryptococci disseminate from the lungs to the brain, causing a deadly meningoencephalitis that is difficult and expensive to treat. Cryptococcal adaptation to the harsh lung environment is a critical first step in its pathogenesis, and consequently a compelling topic of study. This adaptation is mediated by a complex transcriptional program that integrates cellular responses to environmental stimuli...
February 12, 2019: MBio
Shirin Moossavi, Meghan B Azad
No abstract text is available yet for this article.
February 12, 2019: MBio
Pengbo Cao, Xueming Wei, Ram Prasad Awal, Rolf Müller, Daniel Wall
Self-recognition underlies sociality in many group-living organisms. In bacteria, cells use various strategies to recognize kin to form social groups and, in some cases, to transition into multicellular life. One strategy relies on a single genetic locus that encodes a variable phenotypic tag ("greenbeard") for recognizing other tag bearers. Previously, we discovered a polymorphic cell surface receptor called TraA that directs self-identification through homotypic interactions in the social bacterium Myxococcus xanthus Recognition by TraA leads to cellular resource sharing in a process called outer membrane exchange (OME)...
February 12, 2019: MBio
Heyrhyoung Lyoo, Hilde M van der Schaar, Cristina M Dorobantu, Huib H Rabouw, Jeroen R P M Strating, Frank J M van Kuppeveld
The enterovirus genus of the picornavirus family includes a large number of important human pathogens such as poliovirus, coxsackievirus, enterovirus A71, and rhinoviruses. Like all other positive-strand RNA viruses, genome replication of enteroviruses occurs on rearranged membranous structures called replication organelles (ROs). Phosphatidylinositol 4-kinase IIIβ (PI4KB) is required by all enteroviruses for RO formation. The enteroviral 3A protein recruits PI4KB to ROs, but the exact mechanism remains elusive...
February 12, 2019: MBio
Shelly Applen Clancey, Emily J Ciccone, Marco A Coelho, Joie Davis, Li Ding, Renee Betancourt, Samuel Glaubiger, Yueh Lee, Steven M Holland, Peter Gilligan, Julia Sung, Joseph Heitman
The region encompassing the Pacific Northwest (PNW), Vancouver Island, Oregon, and Washington has been the location of an ongoing Cryptococcus gattii outbreak since the 1990s, and there is evidence that the outbreak is expanding along the West Coast into California. Here we report a clinical case of a 69-year-old, HIV-negative man from North Carolina who was diagnosed with a fungal brain mass by magnetic resonance imaging (MRI) and pathology. He had traveled to Seattle and Vancouver 3 years earlier and to Costa Rica 4 months prior to presentation...
February 12, 2019: MBio
Christine Henry, Jizhou Li, François Danion, Laura Alcazar-Fuoli, Emilia Mellado, Rémi Beau, Grégory Jouvion, Jean-Paul Latgé, Thierry Fontaine
Fungal cell wall mannans are complex carbohydrate polysaccharides with different structures in yeasts and molds. In contrast to yeasts, their biosynthetic pathway has been poorly investigated in filamentous fungi. In Aspergillus fumigatus , the major mannan structure is a galactomannan that is cross-linked to the β-1,3-glucan-chitin cell wall core. This polymer is composed of a linear mannan with a repeating unit composed of four α1,6-linked and α1,2-linked mannoses with side chains of galactofuran. Despite its use as a biomarker to diagnose invasive aspergillosis, its biosynthesis and biological function were unknown...
February 12, 2019: MBio
Sara Botto, Jinu Abraham, Nobuyo Mizuno, Kara Pryke, Bryan Gall, Igor Landais, Daniel N Streblow, Klaus J Fruh, Victor R DeFilippis
Secretion of interleukin-1β (IL-1β) represents a fundamental innate immune response to microbial infection that, at the molecular level, occurs following activation of proteolytic caspases that cleave the immature protein into a secretable form. Human cytomegalovirus (HCMV) is the archetypal betaherpesvirus that is invariably capable of lifelong infection through the activity of numerous virally encoded immune evasion phenotypes. Innate immune pathways responsive to cytoplasmic double-stranded DNA (dsDNA) are known to be activated in response to contact between HCMV and host cells...
February 12, 2019: MBio
Felicitas Bossler, Bianca J Kuhn, Thomas Günther, Stephen J Kraemer, Prajakta Khalkar, Svenja Adrian, Claudia Lohrey, Angela Holzer, Mitsugu Shimobayashi, Matthias Dürst, Arnulf Mayer, Frank Rösl, Adam Grundhoff, Jeroen Krijgsveld, Karin Hoppe-Seyler, Felix Hoppe-Seyler
Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia...
February 12, 2019: MBio
David M Hershey, Aretha Fiebig, Sean Crosson
Due to their intimate physical interactions with the environment, surface polysaccharides are critical determinants of fitness for bacteria. Caulobacter crescentus produces a specialized structure at one of its cell poles called the holdfast that enables attachment to surfaces. Previous studies have shown that the holdfast is composed of carbohydrate-based material and identified a number of genes required for holdfast development. However, incomplete information about its chemical structure, biosynthetic genes, and regulatory principles has limited progress in understanding the mechanism of holdfast synthesis...
February 12, 2019: MBio
Bela Hausmann, Claus Pelikan, Thomas Rattei, Alexander Loy, Michael Pester
Microbial diversity in the environment is mainly concealed within the rare biosphere (all species with <0.1% relative abundance). While dormancy explains a low-abundance state very well, the mechanisms leading to rare but active microorganisms remain elusive. We used environmental systems biology to genomically and transcriptionally characterize " Candidatus Desulfosporosinus infrequens," a low-abundance sulfate-reducing microorganism cosmopolitan to freshwater wetlands, where it contributes to cryptic sulfur cycling...
February 12, 2019: MBio
Mrutyunjaya Parida, Kyle A Nilson, Ming Li, Christopher B Ball, Harrison A Fuchs, Christine K Lawson, Donal S Luse, Jeffery L Meier, David H Price
The large genome of human cytomegalovirus (HCMV) is transcribed by RNA polymerase II (Pol II). However, it is not known how closely this betaherpesvirus follows host transcriptional paradigms. We applied PRO-Seq and PRO-Cap methods to profile and quantify transcription initiation and productive elongation across the host and virus genomes in late infection. A major similarity between host transcription and viral transcription is that treatment of cells with the P-TEFb inhibitor flavopiridol preempts virtually all productive elongation, which otherwise covers most of the HCMV genome...
February 12, 2019: MBio
Maggie A Stanislawski, Dana Dabelea, Brandie D Wagner, Nina Iszatt, Cecilie Dahl, Marci K Sontag, Rob Knight, Catherine A Lozupone, Merete Eggesbø
No abstract text is available yet for this article.
February 12, 2019: MBio
Arturo Casadevall
No abstract text is available yet for this article.
February 5, 2019: MBio
Kasie Raymann, Kerri L Coon, Zack Shaffer, Stephen Salisbury, Nancy A Moran
No abstract text is available yet for this article.
February 5, 2019: MBio
Charles L Larson, Kelsi M Sandoz, Diane C Cockrell, Robert A Heinzen
The Q fever agent Coxiella burnetii is a Gram-negative bacterium that invades macrophages and replicates inside a specialized lysosomal vacuole. The pathogen employs a type 4B secretion system (T4BSS) to deliver effector proteins into the host cell that modify the Coxiella- containing vacuole (CCV) into a replication-permissive niche. Mature CCVs are massive degradative organelles that acquire lysosomal proteins. Inhibition of mammalian (or mechanistic) target of rapamycin complex 1 (mTORC1) kinase by nutrient deprivation promotes autophagy and lysosome fusion, as well as activation of the transcription factors TFE3 and TFEB (TFE3/B), which upregulates expression of lysosomal genes...
February 5, 2019: MBio
Matthew J Bush, Govind Chandra, Mahmoud M Al-Bassam, Kim C Findlay, Mark J Buttner
Streptomycetes are filamentous bacteria that differentiate by producing spore-bearing reproductive structures called aerial hyphae. The transition from vegetative to reproductive growth is controlled by the bld (bald) loci, and mutations in bld genes prevent the formation of aerial hyphae, either by blocking entry into development (typically mutations in activators) or by inducing precocious sporulation in the vegetative mycelium (typically mutations in repressors). One of the bld genes, bldC , encodes a 68-residue DNA-binding protein related to the DNA-binding domain of MerR-family transcription factors...
February 5, 2019: MBio
Carlos Pérez-Arques, María Isabel Navarro-Mendoza, Laura Murcia, Carlos Lax, Pablo Martínez-García, Joseph Heitman, Francisco E Nicolás, Victoriano Garre
Mucormycosis is an emerging fungal infection that is often lethal due to the ineffectiveness of current therapies. Here, we have studied the first stage of this infection-the germination of Mucor circinelloides spores inside phagocytic cells-from an integrated transcriptomic and functional perspective. A relevant fungal gene network is remodeled in response to phagocytosis, being enriched in crucial functions to survive and germinate inside the phagosome, such as nutritional adaptation and response to oxidative stress...
February 5, 2019: MBio
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