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https://www.readbyqxmd.com/read/29152583/inhibition-of-retrograde-transport-limits-polyomavirus-infection-in-vivo
#1
Saumya Maru, Ge Jin, Dhimant Desai, Shantu Amin, Shwetank, Matthew D Lauver, Aron E Lukacher
Polyomaviruses (PyVs) silently infect most humans, but they can cause life-threatening diseases in immunocompromised individuals. The JC polyomavirus (JCPyV) induces progressive multifocal leukoencephalopathy, a severe demyelinating disease in multiple sclerosis patients receiving immunomodulatory therapy, and BK polyomavirus (BKPyV)-associated nephropathy is a major cause of kidney allograft failure. No effective anti-PyV agents are available. Several compounds have been reported to possess anti-PyV activity in vitro, but none have shown efficacy in clinical trials...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152582/the-genomic-landscape-of-the-fungus-specific-swi-snf-complex-subunit-snf6-in-candida-albicans
#2
Faiza Tebbji, Yaolin Chen, Adnane Sellam, Malcolm Whiteway
SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and thus represent potential antifungal targets. We have characterized the role of the Snf6 protein in Candida albicans. Our data showed that although there was low conservation of its protein sequence with other fungal orthologs, Snf6 was copurified with bona fide SWI/SNF complex subunits...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152581/the-candida-albicans-tor-activating-gtpases-gtr1-and-rhb1-coregulate-starvation-responses-and-biofilm-formation
#3
Peter R Flanagan, Ning-Ning Liu, Darren J Fitzpatrick, Karsten Hokamp, Julia R Köhler, Gary P Moran
Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in eukaryotic cells and in the fungal pathogen Candida albicans regulates morphogenesis and nitrogen acquisition. Gtr1 encodes a highly conserved GTPase that in Saccharomyces cerevisiae regulates nitrogen sensing and TORC1 activation. Here, we characterize the role of C. albicans GTR1 in TORC1 activation and compare it with the previously characterized GTPase Rhb1. A homozygous gtr1/gtr1 mutant exhibited impaired TORC1-mediated phosphorylation of ribosomal protein S6 and increased susceptibility to rapamycin...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152580/chromosomal-targeting-by-the-type-iii-a-crispr-cas-system-can-reshape-genomes-in-staphylococcus-aureus
#4
Jing Guan, Wanying Wang, Baolin Sun
CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec)...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152579/streptococcus-pneumoniae-tigr4-phase-locked-opacity-variants-differ-in-virulence-phenotypes
#5
Melissa B Oliver, Ankita Basu Roy, Ranjit Kumar, Elliot J Lefkowitz, W Edward Swords
Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity and which allows the population to adapt to different host environments. Generally, transparent variants are adapted for nasopharyngeal colonization, whereas opaque variants are associated with invasive disease. In recent work, colony phase variation was shown to occur by means of recombination events to generate multiple alleles of the hsdS targeting domain of a DNA methylase complex, which mediates epigenetic changes in gene expression...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152578/middle-east-respiratory-syndrome-coronavirus-nonstructural-protein-16-is-necessary-for-interferon-resistance-and-viral-pathogenesis
#6
Vineet D Menachery, Lisa E Gralinski, Hugh D Mitchell, Kenneth H Dinnon, Sarah R Leist, Boyd L Yount, Rachel L Graham, Eileen T McAnarney, Kelly G Stratton, Adam S Cockrell, Kari Debbink, Amy C Sims, Katrina M Waters, Ralph S Baric
Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152577/pseudomonas-aeruginosa-contact-dependent-growth-inhibition-plays-dual-role-in-host-pathogen-interactions
#7
Jeffrey A Melvin, Jordan R Gaston, Shawn N Phillips, Michael J Springer, Christopher W Marshall, Robert M Q Shanks, Jennifer M Bomberger
Microorganisms exist in a diverse ecosystem and have evolved many different mechanisms for sensing and influencing the polymicrobial environment around them, utilizing both diffusible and contact-dependent signals. Contact-dependent growth inhibition (CDI) is one such communication system employed by Gram-negative bacteria. In addition to CDI mediation of growth inhibition, recent studies have demonstrated CDI-mediated control of communal behaviors such as biofilm formation. We postulated that CDI may therefore play an active role in host-pathogen interactions, allowing invading strains to establish themselves at polymicrobial mucosal interfaces through competitive interactions while simultaneously facilitating pathogenic capabilities via CDI-mediated signaling...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152576/meningococcal-antigen-typing-system-mats-based-neisseria-meningitidis-serogroup-b-coverage-prediction-for-the-menb-4c-vaccine-in-the-united-states
#8
Gowrisankar Rajam, Maria Stella, Ellie Kim, Simon Paulos, Giuseppe Boccadifuoco, Laura Serino, George Carlone, Duccio Medini
Neisseria meningitidis is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against N. meningitidis serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States...
November 2017: MSphere
https://www.readbyqxmd.com/read/29134204/latent-membrane-protein-1-is-a-novel-determinant-of-epstein-barr-virus-genome-persistence-and-reactivation
#9
Elizabeth A Caves, Rachel M Butch, Sarah A Cook, Laura R Wasil, Chen Chen, Yuanpu Peter Di, Nara Lee, Kathy H Y Shair
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that persistently infects humans, with nearly 95% seropositivity in adults. Infection in differentiating epithelia is permissive, but EBV-associated nasopharyngeal carcinoma (NPC) tumors harbor a clonal and nonproductive latent infection. However, in explanted NPC cultures and epithelial cell lines, episomal EBV genomes are frequently lost. The resulting unstable infection has hampered efforts to study the determinants of EBV persistence and latency in epithelial oncogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29134203/use-of-multiplex-quantitative-pcr-to-evaluate-the-impact-of-pneumococcal-conjugate-vaccine-on-nasopharyngeal-pneumococcal-colonization-in-african-children
#10
Courtney P Olwagen, Peter V Adrian, Marta C Nunes, Michelle J Groome, Mark F Cotton, Avy Violari, Shabir A Madhi
Pneumococcal conjugate vaccine (PCV) immunization of children induces shifts in colonizing pneumococcal serotypes. This study evaluated the effect of infant vaccination with 7-valent PCV (PCV7) on vaccine serotype (VT) colonization and whether the increase in nonvaccine serotype (NVT) was due to either unmasking of previously low-density-colonizing serotypes or increase in acquisition of NVT. A multiplex quantitative PCR (qPCR) was used to evaluate VT and NVT nasopharyngeal colonization in archived swabs of PCV-vaccinated and PCV-unvaccinated African children at 9 and 15 to 16 months of age...
November 2017: MSphere
https://www.readbyqxmd.com/read/29104937/novel-genes-required-for-the-fitness-of-streptococcus-pyogenes-in-human-saliva
#11
Luchang Zhu, Amelia R L Charbonneau, Andrew S Waller, Randall J Olsen, Stephen B Beres, James M Musser
Streptococcus pyogenes (group A streptococcus [GAS]) causes 600 million cases of pharyngitis each year. Despite this considerable disease burden, the molecular mechanisms used by GAS to infect, cause clinical pharyngitis, and persist in the human oropharynx are poorly understood. Saliva is ubiquitous in the human oropharynx and is the first material GAS encounters in the upper respiratory tract. Thus, a fuller understanding of how GAS survives and proliferates in saliva may provide valuable insights into the molecular mechanisms at work in the human oropharynx...
November 2017: MSphere
https://www.readbyqxmd.com/read/29104936/tuberculosis-state-is-associated-with-expression-of-toll-like-receptor-2-in-sputum-macrophages
#12
Karim Lakehal, David Levine, Kathleen F Kerr, Pooja Vir, Natalie Bruiners, Alfred Lardizabal, Maria Laura Gennaro, Richard Pine
During tuberculosis, macrophages are critical for both pathogen survival and host immune activation. Since expression of particular cell surface markers reflects cell function, we used flow cytometry to measure the abundance of surface markers associated with polarity, lipid uptake, or pattern recognition on macrophages found in induced sputum. Nine macrophage surface markers were examined from three groups of donors: infection-free, latent tuberculosis infection, and active pulmonary tuberculosis. Using a trend test, we found that expression of Toll-like receptor 2 was greater from absence of infection to latent infection and from latent infection to active tuberculosis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29104935/modeling-group-b-streptococcus-and-blood-brain-barrier-interaction-by-using-induced-pluripotent-stem-cell-derived-brain-endothelial-cells
#13
Brandon J Kim, Olivia B Bee, Maura A McDonagh, Matthew J Stebbins, Sean P Palecek, Kelly S Doran, Eric V Shusta
Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs after bacteria interact with and penetrate the blood-brain barrier (BBB). The BBB is comprised of highly specialized brain microvascular endothelial cells (BMECs) that function to separate the circulation from the CNS and act as a formidable barrier for toxins and pathogens. Certain bacteria, such as Streptococcus agalactiae (group B Streptococcus [GBS]), possess the ability to interact with and penetrate the BBB to cause meningitis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29104934/imaging-the-antistaphylococcal-activity-of-cath-2-mechanism-of-attack-and-regulation-of-inflammatory-response
#14
Viktoria A F Schneider, Maarten Coorens, Johanna L M Tjeerdsma-van Bokhoven, George Posthuma, Albert van Dijk, Edwin J A Veldhuizen, Henk P Haagsman
Chicken cathelicidin-2 (CATH-2) is a broad-spectrum antimicrobial host defense peptide (HDP) that may serve as a paradigm for the development of new antimicrobial agents. While previous studies have elucidated the mechanism by which CATH-2 kills Escherichia coli, its mode of action against Gram-positive bacteria remains to be determined. In this study, we explored the underlying antibacterial mechanism of CATH-2 against a methicillin-resistant strain of Staphylococcus aureus and the effect of CATH-2-mediated S...
November 2017: MSphere
https://www.readbyqxmd.com/read/29104933/heat-resistance-mediated-by-plm58-plasmid-borne-clpl-in-listeria-monocytogenes
#15
Anna Pöntinen, Mariella Aalto-Araneda, Miia Lindström, Hannu Korkeala
Listeria monocytogenes is one of the most heat-resistant non-spore-forming food-borne pathogens and poses a notable risk to food safety, particularly when mild heat treatments are used in food processing and preparation. While general heat stress properties and response mechanisms of L. monocytogenes have been described, accessory mechanisms providing particular L. monocytogenes strains with the advantage of enhanced heat resistance are unknown. Here, we report plasmid-mediated heat resistance of L. monocytogenes for the first time...
November 2017: MSphere
https://www.readbyqxmd.com/read/29104932/multidrug-resistant-salmonella-enterica-serovar-typhimurium-isolates-are-resistant-to-antibiotics-that-influence-their-swimming-and-swarming-motility
#16
Brian W Brunelle, Bradley L Bearson, Shawn M D Bearson, Thomas A Casey
Motile bacteria employ one or more methods for movement, including darting, gliding, sliding, swarming, swimming, and twitching. Multidrug-resistant (MDR) Salmonella carries acquired genes that provide resistance to specific antibiotics, and the goal of our study was to determine how antibiotics influence swimming and swarming in such resistant Salmonella isolates. Differences in motility were examined for six MDR Salmonella enterica serovar Typhimurium isolates grown on swimming and swarming media containing subinhibitory concentrations of chloramphenicol, kanamycin, streptomycin, or tetracycline...
November 2017: MSphere
https://www.readbyqxmd.com/read/29085913/plasticity-of-the-mfs1-promoter-leads-to-multidrug-resistance-in-the-wheat-pathogen-zymoseptoria-tritici
#17
Selim Omrane, Colette Audéon, Amandine Ignace, Clémentine Duplaix, Lamia Aouini, Gert Kema, Anne-Sophie Walker, Sabine Fillinger
The ascomycete Zymoseptoria tritici is the causal agent of Septoria leaf blotch on wheat. Disease control relies mainly on resistant wheat cultivars and on fungicide applications. The fungus displays a high potential to circumvent both methods. Resistance against all unisite fungicides has been observed over decades. A different type of resistance has emerged among wild populations with multidrug-resistant (MDR) strains. Active fungicide efflux through overexpression of the major facilitator gene MFS1 explains this emerging resistance mechanism...
September 2017: MSphere
https://www.readbyqxmd.com/read/29085912/gene-acquisition-by-a-distinct-phyletic-group-within-streptococcus-pneumoniae-promotes-adhesion-to-the-ocular-epithelium
#18
Irena Antic, Kimberly M Brothers, Maureen Stolzer, Han Lai, Evan Powell, Rory Eutsey, Rolando A Cuevas, Xinyu Miao, Regis P Kowalski, Robert M Q Shanks, Dannie Durand, N Luisa Hiller
Streptococcus pneumoniae (pneumococcus) displays broad tissue tropism and infects multiple body sites in the human host. However, infections of the conjunctiva are limited to strains within a distinct phyletic group with multilocus sequence types ST448, ST344, ST1186, ST1270, and ST2315. In this study, we sequenced the genomes of six pneumococcal strains isolated from eye infections. The conjunctivitis isolates are grouped in a distinct phyletic group together with a subset of nasopharyngeal isolates. The keratitis (infection of the cornea) and endophthalmitis (infection of the vitreous body) isolates are grouped with the remainder of pneumococcal strains...
September 2017: MSphere
https://www.readbyqxmd.com/read/29062900/microbiota-diversification-and-crash-induced-by-dietary-oxalate-in-the-mammalian-herbivore-neotoma-albigula
#19
Aaron W Miller, Colin Dale, M Denise Dearing
Oxalate, broadly found in both dietary and endogenous sources, is a primary constituent in 80% of kidney stones, an affliction that has tripled in prevalence over the last 40 years. Oxalate-degrading bacteria within the gut microbiota can mitigate the effects of oxalate and are negatively correlated with kidney stone formation, but bacteriotherapies involving oxalate-degrading bacteria have met with mixed results. To inform the development of more effective and consistent bacteriotherapies, we sought to quantify the interactions and limits between oxalate and an oxalate-adapted microbiota from the wild mammalian herbivore Neotoma albigula (woodrat), which consumes a high-oxalate diet in the wild...
September 2017: MSphere
https://www.readbyqxmd.com/read/29062899/differential-roles-for-inner-membrane-complex-proteins-across-toxoplasma-gondii-and-sarcocystis-neurona-development
#20
Rashmi Dubey, Brooke Harrison, Sriveny Dangoudoubiyam, Giulia Bandini, Katherine Cheng, Aziz Kosber, Carolina Agop-Nersesian, Daniel K Howe, John Samuelson, David J P Ferguson, Marc-Jan Gubbels
The inner membrane complex (IMC) of apicomplexan parasites contains a network of intermediate filament-like proteins. The 14 alveolin domain-containing IMC proteins in Toxoplasma gondii fall into different groups defined by their distinct spatiotemporal dynamics during the internal budding process of tachyzoites. Here, we analyzed representatives of different IMC protein groups across all stages of the Toxoplasma life cycle and during Sarcocystis neurona asexual development. We found that across asexually dividing Toxoplasma stages, IMC7 is present exclusively in the mother's cytoskeleton, whereas IMC1 and IMC3 are both present in mother and daughter cytoskeletons (IMC3 is strongly enriched in daughter buds)...
September 2017: MSphere
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