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Virulence Regulation

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https://www.readbyqxmd.com/read/29150513/high-prevalence-and-genetic-diversity-of-large-phicd211-phicdif1296t-like-prophages-in-clostridioides-difficile
#1
Julian R Garneau, Ognjen Sekulovic, Bruno Dupuy, Olga Soutourina, Marc Monot, Louis-Charles Fortier
Clostridioides difficile (formerly Clostridium difficile) is a pathogenic bacterium displaying great genetic diversity. A significant proportion of this diversity is due to the presence of integrated prophages. Here, we provide an in-depth analysis of phiCD211, also known as phiCDIF1296T, the largest phage identified in C. difficile so far, with a genome of 131-kbp. It shares morphological and genomic similarity with other large siphophages like phage 949 infecting Lactococcus lactis and phage c-st infecting Clostridium botulinum...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150501/glna-truncation-in-salmonella-enterica-results-in-a-small-colony-variant-phenotype-attenuated-host-cell-entry-and-reduced-expression-of-flagellin-and-spi-1-associated-effector-genes
#2
Philipp Aurass, Juliane Düvel, Susanne Karste, Ulrich Nübel, Wolfgang Rabsch, Antje Flieger
Many pathogenic bacteria use sophisticated survival strategies to overcome harsh environmental conditions. One is the formation of slow-growing subpopulations termed small colony variants (SCVs). Here we characterize an SCV, which spontaneously emerged from an axenic Salmonella enterica serovar Typhimurium water culture. We found that the SCV harbors a frameshift mutation in the glutamine synthetase gene glnA leading to a ∼90% truncation of the corresponding protein. Glutamine synthetase, a central enzyme in nitrogen assimilation, converts glutamate and ammonia to glutamine...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29149170/vibrio-parahaemolyticus-vtra-is-a-membrane-bound-regulator-and-is-activated-via-oligomerization
#3
Ryu Okada, Shigeaki Matsuda, Tetsuya Iida
Vibrio parahaemolyticus is a Gram-negative pathogen that causes food-borne gastroenteritis. A major virulence determinant of the organism is a type III secretion system (T3SS2) encoded on a pathogenicity island, Vp-PAI. Vp-PAI gene expression is regulated by two transcriptional regulators, VtrA and VtrB, whose N-terminal regions share homology with an OmpR-family DNA-binding domain. VtrA activates the gene expression of VtrB, which in turn activates Vp-PAI gene expression; however, the mechanism of this transcriptional activation by VtrA is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/29149107/treponema-denticola-chymotrypsin-like-proteinase-may-contribute-to-orodigestive-carcinogenesis-through-immunomodulation
#4
Mikko T Nieminen, Dyah Listyarifah, Jaana Hagström, Caj Haglund, Daniel Grenier, Dan Nordström, Veli-Jukka Uitto, Marcela Hernandez, Tülay Yucel-Lindberg, Taina Tervahartiala, Mari Ainola, Timo Sorsa
BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29145803/unraveling-the-evolution-and-coevolution-of-small-regulatory-rnas-and-coding-genes-in-listeria
#5
Franck Cerutti, Ludovic Mallet, Anaïs Painset, Claire Hoede, Annick Moisan, Christophe Bécavin, Mélodie Duval, Olivier Dussurget, Pascale Cossart, Christine Gaspin, Hélène Chiapello
BACKGROUND: Small regulatory RNAs (sRNAs) are widely found in bacteria and play key roles in many important physiological and adaptation processes. Studying their evolution and screening for events of coevolution with other genomic features is a powerful way to better understand their origin and assess a common functional or adaptive relationship between them. However, evolution and coevolution of sRNAs with coding genes have been sparsely investigated in bacterial pathogens. RESULTS: We designed a robust and generic phylogenomics approach that detects correlated evolution between sRNAs and protein-coding genes using their observed and inferred patterns of presence-absence in a set of annotated genomes...
November 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29143814/structural-basis-of-nucleotide-sugar-transport-across-the-golgi-membrane
#6
Joanne L Parker, Simon Newstead
Glycosylation is a fundamental cellular process that, in eukaryotes, occurs in the lumen of both the Golgi apparatus and the endoplasmic reticulum. Nucleotide sugar transporters (NSTs) are an essential component of the glycosylation pathway, providing the diverse range of substrates required for the glycosyltransferases. NSTs are linked to several developmental and immune disorders in humans, and in pathogenic microbes they have an important role in virulence. How NSTs recognize and transport activated monosaccharides, however, is currently unclear...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29137267/tumacrophage-macrophages-transformed-into-tumor-stem-like-cells-by-virulent-genetic-material-from-tumor-cells
#7
Yizhuang Zhang, Na Zhou, Xiuyan Yu, Xuehui Zhang, Shanxin Li, Zhen Lei, Ruobi Hu, Hui Li, Yiqing Mao, Xi Wang, Jinshu Zhang, Yuan Li, Hongyan Guo, David M Irwin, Gang Niu, Huanran Tan
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135911/the-apoptogenic-toxin-aip56-is-secreted-by-the-type-ii-secretion-system-of-photobacterium-damselae-subsp-piscicida
#8
Ana do Vale, Cassilda Pereira, Carlos R Osorio, Nuno M S Dos Santos
AIP56 (apoptosis-inducing protein of 56 kDa) is a key virulence factor of Photobacterium damselae subsp. piscicida (Phdp), the causative agent of a septicaemia affecting warm water marine fish species. Phdp-associated pathology is triggered by AIP56, a short trip AB toxin with a metalloprotease A domain that cleaves the p65 subunit of NF-κB, an evolutionarily conserved transcription factor that regulates the expression of inflammatory and anti-apoptotic genes and plays a central role in host responses to infection...
November 14, 2017: Toxins
https://www.readbyqxmd.com/read/29134812/deoxycholate-enhanced-shigella-virulence-is-regulated-by-a-rare-%C3%AF-helix-in-the-type-three-secretion-system-tip-protein-ipad
#9
Abram R Bernard, T Carson Jessop, Prashant Kumar, Nicholas E Dickenson
Type three secretion systems (T3SS) are specialized nano-machines that support infection by injecting bacterial proteins directly into host cells. The Shigella T3SS has uniquely evolved to sense environmental levels of the bile salt deoxycholate (DOC) and up-regulate virulence in response to DOC. In this study, we describe a rare i+5 hydrogen bonding secondary structure element (π-helix) within the type three secretion system tip protein IpaD that plays a critical role in DOC-enhanced virulence. Specifically, engineered mutations within the π-helix altered the pathogen's response to DOC with one mutant construct in particular exhibiting an unprecedented reduction in virulence following DOC exposure...
November 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/29133401/multiple-legionella-pneumophila-effector-virulence-phenotypes-revealed-through-high-throughput-analysis-of-targeted-mutant-libraries
#10
Stephanie R Shames, Luying Liu, James C Havey, Whitman B Schofield, Andrew L Goodman, Craig R Roy
Legionella pneumophila is the causative agent of a severe pneumonia called Legionnaires' disease. A single strain of L. pneumophila encodes a repertoire of over 300 different effector proteins that are delivered into host cells by the Dot/Icm type IV secretion system during infection. The large number of L. pneumophila effectors has been a limiting factor in assessing the importance of individual effectors for virulence. Here, a transposon insertion sequencing technology called INSeq was used to analyze replication of a pool of effector mutants in parallel both in a mouse model of infection and in cultured host cells...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29133345/small-rna-teg49-is-derived-from-a-sara-transcript-and-regulates-virulence-genes-independent-of-sara-in-staphylococcus-aureus
#11
Adhar C Manna, Samin Kim, Liviu Cengher, Anna Corvaglia, Stefano Leo, Patrice Francois, Ambrose L Cheung
Expression of virulence factors in S. aureus is regulated by a wide range of transcriptional regulators including proteins and small RNAs (sRNAs) at the level of transcription and/or translation. The sarA locus consists of three overlapping transcripts generated from three distinct promoters, all encoding the sarA ORF. The 5' UTRs of these transcripts contain three separate regions at ∼711, 409, and 146-nt upstream of the sarA translation start, the functions of which remain unknown. Recent RNA-Seq analysis and subsequent characterization indicated that two sRNA, teg49 and teg48, are processed and likely produced from the sarA P3 and sarA P1 transcripts of the sarA locus, respectively...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29133150/structure-and-function-of-per-arnt-sim-domains-and-their-possible-role-in-the-life-cycle-biology-of-trypanosoma-cruzi
#12
REVIEW
Maura Rojas-Pirela, Daniel J Rigden, Paul A Michels, Ana J Cáceres, Juan Luis Concepción, Wilfredo Quiñones
Per-ARNT-Sim (PAS) domains of proteins play important roles as modules for signalling and cellular regulation processes in widely diverse organisms such as Archaea, Bacteria, protists, plants, yeasts, insects and vertebrates. These domains are present in many proteins where they are used as sensors of stimuli and modules for protein interactions. Characteristically, they can bind a broad spectrum of molecules. Such binding causes the domain to trigger a specific cellular response or to make the protein containing the domain susceptible to responding to additional physical or chemical signals...
November 10, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29132819/quorum-sensing-systems-as-targets-for-antivirulence-therapy
#13
REVIEW
Tom Defoirdt
The development of novel therapies to control diseases caused by antibiotic-resistant pathogens is one of the major challenges we are currently facing. Many important plant, animal, and human pathogens regulate virulence by quorum sensing, bacterial cell-to-cell communication with small signal molecules. Consequently, a significant research effort is being undertaken to identify and use quorum-sensing-interfering agents in order to control diseases caused by these pathogens. In this review, an overview of our current knowledge of quorum-sensing systems of Gram-negative model pathogens is presented as well as the link with virulence of these pathogens, and recent advances and challenges in the development of quorum-sensing-interfering therapies are discussed...
November 10, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29132313/comparative-transcriptome-analysis-of-a-lowly-virulent-strain-of-erwinia-amylovora-in-shoots-of-two-apple-cultivars-susceptible-and-resistant-to-fire-blight
#14
Joanna Puławska, Monika Kałużna, Wojciech Warabieda, Artur Mikiciński
BACKGROUND: Erwinia amylovora is generally considered to be a homogeneous species in terms of phenotypic and genetic features. However, strains show variation in their virulence, particularly on hosts with different susceptibility to fire blight. We applied the RNA-seq technique to elucidate transcriptome-level changes of the lowly virulent E. amylovora 650 strain during infection of shoots of susceptible (Idared) and resistant (Free Redstar) apple cultivars. RESULTS: The highest number of differentially expressed E...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29130383/identification-of-a-novel-gene-in-rod9-island-of-salmonella-enteritidis-involved-in-the-alteration-of-virulence-associated-genes-expression
#15
Susmita Das, Shilpa Ray, Daniel Ryan, Bikash Sahu, Mrutyunjay Suar
Salmonella enterica subsp. I serovar Enteritidis (S. Enteritidis), one of the causative agents for non-typhoidal gastrointestinal diseases in humans is an intracellular bacterium and mechanism for its invasion into host cells is critical to cause infection. The virulence of the pathogen is explained by the expression of genes located on its pathogenicity islands, mostly encoded under SPI-1 and SPI-2. However, S. Typhimurium SL1344, despite sharing ∼98% of its genome with S. Enteritidis P125109, lacks few regions of differences (ROD) that are hypothesized to impart virulence potential to S...
November 13, 2017: Virulence
https://www.readbyqxmd.com/read/29130186/identification-of-staphylococcal-quorum-sensing-inhibitors-by-quantification-of-%C3%A3%C2%B5-hemolysin-with-high-performance-liquid-chromatography
#16
Cassandra L Quave, Alexander R Horswill
Quorum sensing plays a major role in regulation of virulence factor production by staphylococci. Chemical inhibitors that block this process and prevent the production of exotoxins and exoenzymes could have medical utility for infection prophylaxis and therapy. Here, we describe a high performance liquid chromatography method amenable to medium throughput screening for staphylococcal quorum sensing inhibitors by quantification of õ-hemolysin, a direct protein output of this system.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29130185/identification-of-ai-2-quorum-sensing-inhibitors-in-vibrio-harveyi-through-structure-based-virtual-screening
#17
Tianyu Jiang, Peng Zhu, Lupei Du, Minyong Li
Quorum sensing (QS) is a cell-to-cell communication system that regulates gene expression as a result of the production and perception of signal molecules called autoinducers (AIs). AI-2 is a QS autoinducer produced by both Gram-negative and Gram-positive bacteria, in which it regulates intraspecies and interspecies communication. The identification of QS inhibitors is considered a promising strategy for the development of anti-virulence drugs with reduced selective pressure for resistance. Here we describe a high-throughput virtual screening approach to identify AI-2 quorum sensing inhibitors on the basis of Vibrio harveyi LuxPQ crystal structure...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29130180/qualitative-and-quantitative-determination-of-quorum-sensing-inhibition-in-vitro
#18
Tim Holm Jakobsen, Maria Alhede, Louise Dahl Hultqvist, Thomas Bjarnsholt, Michael Givskov
The formation of biofilms in conjunction with quorum sensing (QS) regulated expression of virulence by opportunistic pathogens contributes significantly to immune evasion and tolerance to a variety of antimicrobial treatments. The present protocol describes methods to determine the in vitro efficacy of potential QS inhibitors (QSIs). Work on Pseudomonas aeruginosa has shown that chemical blockage of QS is a promising new antimicrobial strategy. Several live bacterial reporter systems have been developed to screen extracts and pure compounds for QSI activity...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29130178/methods-to-study-quorum-sensing-dependent-virulence-and-movement-of-phytopathogens-in-planta
#19
Shulamit Manulis-Sasson, Laura Chalupowicz
Cell-to-cell communication mediated by the diffusible signal factor (DSF) is a common form of gene regulation and plays an important role in virulence of many plant pathogenic bacteria including Xanthomonas spp. Here we describe several approaches to study the involvement of DSF-dependent QS system of the plant pathogenic bacteria Xanthomonas campestris pv. pelargonii (Xhp) as an example of the Xanthomonas spp. The methods described include detection and measurement of DSF, movement in planta, colonization, and aggregate formation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29130160/use-of-whole-cell-bioassays-for-screening-quorum-signaling-quorum-interference-and-biofilm-dispersion
#20
Starla G Thornhill, Robert J C McLean
In most bacteria, a global level of regulation, termed quorum sensing (QS), exists involving intercellular communication via the production and response to cell density-dependent signal molecules. QS has been associated with a number of important features in bacteria including virulence regulation and biofilm formation. Consequently, there is considerable interest in understanding, detecting, and inhibiting QS. N-acylated homoserine lactones (AHLs) are used as extracellular QS signals by a variety of Gram-negative bacteria...
2018: Methods in Molecular Biology
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