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166 Cards in this Set
- Front
- Back
Where would you find Bacillus cereus |
Rice and survives heating |
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What is Bacillus mycoides? |
Insect pathogen |
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Bacillus are |
Aerobic and facultative anaerobic formers |
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The two most common examples of bacteria that are known to form endospores |
Bacillus and clostridium |
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Clostridium are |
Strict anaerobic spore formers |
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Clostridium botulinum produces .... Under .... |
Botulinum toxin under low-oxygen conditions |
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What is the most commonly diagnosed bacterial cause of hospital acquired infectious diarrhea? |
Clostridium difficile |
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What is normally the cause of C. diff |
Antibiotics |
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How would you describe c.diff |
Anaerobic spore forming motile gram positive rod |
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What does C.diff look like on blood agar? |
Irregular white colonies |
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Spores are resistant to |
Drying, heating, chemicals and radiation |
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What is the response regulator that drives sporulation in C.diff |
SpoOA |
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In limited nutrient environment sporulation in C.diff is initiated by |
Sensor histidine kinases |
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In c.diff sporulation histidine kinases phosphorylate |
Spo0A |
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Phosphorylated SpoOA induces expression of |
Sigma factor, sigmaH which forms a positive feed-forward loop with Spo0A |
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In c.diff sporulation, SpoOA drives the sequential activation of four sigma factors called |
Sigma F, E, G, K |
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Germination of the C.diff spore can be initiated by |
Bile acids, taurocholate which signals through the CspC receptor |
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In c.diff sporulation, when bile acids bind to the cspC receptor what does this activate and what does it lead to ? |
SleC enzyme through CspB , leads to the degradation of the proteoglycan spore cortex |
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Addition of taurocholate to CCF agar does what to c.diff? |
Increases recovery of colonies from spores |
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Vegetative growth of C.diff colonies can be inhibited by? |
Secondary bile acids |
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The ability of C.difd to cause colitis depends on what types of virulence factors ? |
Toxins, adherence and motility factors |
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What is colitis? |
Inflammation and irritation of the colon and rectum |
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What cells do C.diff toxins primarily target? |
Intestinal epithelial cells |
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Toxin endocytosis and activation in the cytosol of epithelial cells causes necrosis which leads to (3) |
- Loss of intestinal membrane integrity - Host exposure to intestinal microorganisms - Activation of the host inflammatory response |
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What is a pathogenicity locus? |
A group of genes that are responsible for the virulence factors that help cause disease |
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How many toxins does C.diff produce and what are they? |
TcdA TcdB Binary toxin (CDT) |
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The pathogenicity locus in C.diff encodes how many proteins? |
5 |
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What is TcdA? |
An enterotoxin produced by C.diff |
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What is TcdB? |
A potent cytotoxin produced by C.diff |
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What are the domains within TcdA and TcdB? |
Glucosyl transferase domains Cysteine protease domain Hydrophobic protein sequence Combined repetitive oligopeptide repeat |
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What's does RHO and RAC glucosyl transferase domains at the N terminus of TcdA/B do? |
Mediate toxicity by glycosylation and inactivating host RHO and RAC GTPases Breakdown of tight junctions, cytoskeleton and epithelial integrity |
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What does the cysteine protease domain in tcdA/B do? |
Autocatalytically cleaves binary toxin in the cytosol of eukaryotic cells in association with myo-inositol |
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What is the hydrophobic protein sequence in TcdA/B involved in? |
Host cell membrane insertion |
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What is the combined repetitive oligopeptide repeat domain thought to bind to in TcdA/B? |
Cell surface receptors before endocytosis and internalisation of TcdA and TcdB |
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What is TcdR? |
An alternative sigma factor that facilitates the binding of RNA polymerase to the promoters of the tcdA and tcdB |
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What is tcdC? |
It is expressed during the growth of C.diff and is thought to act as an anti-sigma factor and thus suppress tcdA and tcdB transcription |
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What is tcdE? |
Is a holin-like protein that is thought to facilitate the secretion of tcdA and tcdB which lack conventional secretion signal sequences |
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What strains of C. diff produce binary toxin? |
Hypervirulent |
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How many domains is CDT composed of and what are they? |
Two proteins/domains CdtA and CdtB |
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What is CdtA? |
An ADP-ribosyl transferase that ribosylates actin in eukaryotic cells potentially interfering with actin polymerization and cytoskeletal structure |
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What does CdtB do? |
Forms pores in acidified endosomes and facilitates the transfer of CdtA to the cytosol |
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Lack of flagella in C.diff is associated with |
Impaired adherence to the intestinal epithelium |
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Mutants (c.diff) that lack a flagella also exhibit |
Dysregulated toxin expression and virulence in vivo |
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Flagellum expression in C.diff is regulated by which intracellular nessenger |
C-di-GMP |
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C-di-GMP is a key signal that switches C.diff between a ....... and a |
Motile, toxin producing state and a adherent biofilm producing state |
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High levels of intracellular c-di-GMP do what? |
Repress flagellum expression Repress the synthesis of tcdA and TcdB Induce the expression of pili that interact with intestinal epithelium |
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What proteins contribute to the adherence and biofilm formation in C.diff? |
Adhesion fibronectin binding protein A Cwp66 and Cwp84 S-layer protein Spo0A |
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The extracellular matrix of a biofilm is composed of |
Proteins Polysaccharides Free DNA from dead cells |
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What does TcdB do to host ? |
Activates a calcium influx causing disintegration of the actin cytoskeleton |
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What does tcdA do to host? |
Inhibits stimulated mucin exocytosis |
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What leads to C.diff pathogenesis |
Release of inflammatory cytokines which recruit neutrophils |
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C.diff toxins increase the release of ....? What does it do? |
Substance P Enhances fluid loss from the intestines and decreases the exocytosis of the protective mucus barrier |
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What bacteria normally dominate the stomach? |
Lactobacillus Streptococcus |
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What bacteria normally dominate the distal gut? |
Bacteroides and clostridium |
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What increases your odds of getting c.diff? (apart from antibiotics) |
A condition such as colorectal cancer or inflammatory bowel disease A weakened immune system caused by cancer treatment or another health problem |
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What are the microbiomes defenses against C.diff? 2 |
- Microbiota converts primary bile acids into secondary bile acids which inhibit the growth of c.diff - Commensal bacteria species convert sialic acid attached to epithelial cells into energy |
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Antibiotics disruption of microbiota depletes .... enabling |
Primary bile acid converters enabling c.diff sporulation and growth |
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Good igG/A response to C.diff toxins indicate |
Asymptomatic carrier |
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Poor igG/A response to C.diff toxins indicates ....... |
Immunodeficiency |
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Poor immune response to c.diff will lead to (4) |
Production of toxins Activation of macrophages Upregulation of cytokines and other mediators of inflammation Clinical disease |
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What is PMC in C.diff? |
Pseudomembranous colitis |
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Infection with C.diff can range from |
C.diff associated disease Pseudomembranous colitis |
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How can C.diff be diagnosed? (7 ways) |
- Detection of toxins in faeces by ELISA - Detection of glutamate dehydrogenase in feces using antibodies - Culture anaerobically on agar - Ribotyping - PCR - Colonoscopy - Genome sequencing |
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When would you use a colonoscopy to detect c.diff? |
Is pseudomembranous colitis is suspected |
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What is ribotyping? |
A molecular technique for bacterial id and characterization that uses information from rRNA-based phylogenetic analyses |
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Treatment of C.diff? (5 ways) |
- Discontinuing implicated antibiotic - Treatment with counter antibiotics - intravenous ig - probiotic/ faecal enema -Faecal transplant |
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Enteric bacteria are.... |
Facultative aerobes gram-negative Non-sporulating Rods |
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What biochemical tests can be used to distinguish enteric bacteria from other gammaproteobacteria? |
Oxidase test Catalase test |
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Enteric bacteria result on oxidase test |
Negative |
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Enteric bacteria result on catalase test |
Positive |
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Salmonella and shigella can be distinguished based on (3) |
Various biochemical tests - most salmonella produce hydrogen sulphide Motility - salmonella are peritrichously flagellated Host range |
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What agar can be used to distinguish salmonella and shigella |
Hektoen enteric agar |
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What salmonella species is responsible for the majority of disease seen in humans? |
S. enterica |
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What salmonella species infectes cold-blooded animals ? |
S. bongeri |
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Serovars/serotypes of salmonella are based on? |
Three major antigens O, H and Vi capsule |
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What is the O antigen in salmonella? |
The outermost portion of the bacteria's surface (LPS)
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What is the H antigen in salmonella? |
A slender threadlike structure that is part of the flagella |
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What morphology and gram stain does salmonella have? |
Gram negative rod |
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What kind of bacteria is shigella? |
Gram-negative, non-motile, facultatively anaerobic, non-spore forming rod |
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What are the three major species of shigella that cause disease? |
S.flexneri S. Sonnei S.dysenteriae |
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What are salmonella and shigellas key virulence factors? (5) |
Endotoxin Exotocin Type 3 Secretion system Flagella and pili Biofilm formation |
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How can bacterial virulence factors be acquired? (2) |
Horizontal gene transfer to pathogenicity islands or plasmids Prophages |
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Salmonella and shigella both use ..... to enter cells |
Trigger mechanism |
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What is the trigger mechanism? |
Bacterial effector proteins secreted via the type 3 secretion system activate signalling pathways that dynamically modify the cytoskeleton underlying the membrane, creating membrane ruffles that engulf the pathogen |
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What is used by some bacteria as an alternative to the trigger method? |
Zipper method |
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What are type 3 secretion systems? |
T3SS are complex bacterial structures that allow gram neg bacteria to inject bacterial effector proteins directly into the host cell cytosol |
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Proteins in T3SS are related to what other bacteria structure |
Flagellar motor |
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How does salmonella survive life in the phagosome? |
Injects effector proteins in to the cytoplasm which then modify the surface of the salmonella containing vacuole which blocks fusion with the lysosome |
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How does shigella avoid killing by the phagosome? |
It escapes into the cytosol by bursting the phagosome |
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What do bacteria have to develop strategies for? |
Nutrient acquisition Motility Transmission |
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How does shigella escape the phagosome? |
IpaB and IpaC along with host factors interact with the vesicle membrane and destabilise it |
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How does shigella spread between cells? |
Actin mobility |
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How does actin mobility in shigella work? |
Bacterial protein IcsA, expressed on bacterial pole surface, binds and activates protein called N-WASP which then activated the Arp2/3 complex causing actin polymerisation |
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During intercellular spread, actin polymerization at the bacterial surface generates ... |
Protrusions of the plasma membrane which are engulfed by adjacent cells |
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How are bacterial exotoxins classified? |
They can be classified into three types based on their mode of action Type 1- superantigens Type 2 - membrane disrupting toxins Type 3 - A/B toxins and other toxins that interfere with host cell function |
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What is an enterotoxin? |
Exotoxins whose site of action is in the small intestine leading to fluid accumulation and diarrhoea |
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How many enterotoxins does shigella produce and what are they? |
ShET1 ShET2 |
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What toxin is specific to shigella dysenteriae and some species of Ecoli? |
Shiga toxin |
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Where is ShET1 encoded? |
Pathogenicity island SHI-1 |
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Where is ShET2 encoded? |
Virulence plasmid |
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Where is Shiga toxin encoded in shigella? |
Bacteriophage genome that is integrated into the circular bacterial chromosome or extrachromosomal plasmid |
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How does shiga toxin enter a cell? |
It attaches vie ganglioside Gb3 and is then taken in by receptor mediated endocytosis |
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What is Shiga toxin mechanism of action? |
Once inside the cell it cleaves 28S rRNA to interfere and stop host cell translation |
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What is the causative agent of diarrhoea in salmonella? |
Salmonella enterotoxin |
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Why does s.typhi LPS not trigger host inflammatory response |
It has gained a pathogenicity island (SP17) along with a capsule biosynthesis locus (Vi antigen) The Vi antigen masks the LPS
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What allows salmonella to outgrow normal guy microbiota? |
Tetrathionate metabolism |
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What groups is salmonella enterica split into to? |
Typhoidal serovars and non-typhoidal serovars |
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How does tetrathionate metabolism work? |
- Hydrogen sulphide is produced by the microbiota which is then detoxified to thiosulfate by intestinal epithelial cells - Salmonella then induced inflammation and neutrophils are recruited - neutrophils produce ROS which oxidise thiosulphate to tetrathionate - salmonella can use tetrathionate during metabolism |
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What genes allow salmonella to use tetrathionate during metabolism? |
SPI-2 |
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What is the first stage in salmonella pathogenesis? |
SPI-1 effector proteins are injected by salmonella T3SS into host M cells |
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What is the first stage in shigella pathogenesis? |
Shigella traverses the colonic epithelial barrier through M cells where it is then phagocytosed by antigen-presenting cells |
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Cytosolic replication of shigella is facilitated through ... |
The injection of a second wave of T3SS effectors that function to damp the host inflammatory response, promote host cell survival and counteract antimicrobial processes |
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How are shigella and salmonella transmitted? |
Fecal-oral route |
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Does salmonella or shigella have a smaller infectious does? |
Shigella |
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What salmonella can reside in the gallbladder even after infection? |
Salmonella typhi |
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How can typhoid fever be treated? |
Antibiotics - where antibiotic resistance is uncommon - a fluoroquinolone - otherwise, a third generation cephalosporin |
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An example of a fluoroquinolone? |
Ciprofloxacin |
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An example of a cephalosporin |
Ceftriaxone |
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What do fluoroquinolones target? |
DNA gyrase |
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What are cephalosporins? |
Beta-lactam antibiotic |
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How to treat diarrhoeal diseases? |
Rehydration therapy - replacing fluids and salts Occasionally antibiotics therapy |
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What are the 5 main genera in the picornaviridae? |
Enterovirus Aphthovirua Heparnavirus Cardiovirus Parechovirus |
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Enteroviruses examples (4) |
Polio virus Coxsackie virus Echovirus Rhinovirus |
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What is rhinovirus? |
Major cause of the common cold |
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What does aphthovirus cause? |
Foot and mouth disease |
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Structure of picornaviruses |
Icosahedral capsid - 4 viron polypeptides assemble into protoner subunits - 5 of these subunits assemble into pentamers - 12 pentamers then associate to form the procapsid |
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What is the receptor binding site for a picornavirus? |
Cayon |
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Picornavirus genome |
Single strand +ve sense RNA - small protein, VPg, attached to 5' end and polyA tail |
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Picornavirus replication |
- viron binds to host cell and is internalised - VP4 exists the virus and interacts with host cell liposomes, inducing membrane permeability by forming a multimeric pore - viral genome is injected through this pore into host cell cytosole -injected genome is translated into a polyprotein - RNA replicase is then cleaved off of the polyprotein and goes on to replicate new genome |
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Assembly of poliovirus particles |
-structural proteins VP0, VP1 and VP3 are cleaved from the translated polyprotein by proteases - VP0, VP1 and VP3 assemble into protomer subunits - 5 subunits then assemble into pentamers - 12 pentamers associate to form procapsid - Genome is inserted |
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How are VP4 and VP2 formed in picornoviruses? |
Cleavage of VP0 |
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How are enteroviruses transmitted? |
Faecal-oral route |
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Primary infection site for enteroviruses? |
Upper respiratory tract |
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What family do enteroviruses belong to? |
Picornoviridae |
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Clinical presentation of enteroviruses depends on? (6) |
Tissue tropism Viral serotype Infecting dose Entry portal Patients age, sex and health Pregnancy |
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What is a cytolytic virus? |
Virus kills host cell after viral replication |
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What play a major role in protective response to enteroviruses? |
Antibodies |
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Infections with poliovirus range from? (4 types) |
Asymptomatic illness Abortive poliomyelitis Non-paralytic poliomyelitis Paralytic polio |
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What is abortive poliomyelitis? How many does it infect? |
Flu like symptoms that last for 2 to 3 days 5% |
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What is non-paralytic poliomyelitis? |
Sever flu-like symptoms, neck pain/stiffness in arms or less, severe headache |
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What is paralytic polio? How many does it infect? |
Infection of the nerve tissue Less than 1% of infections |
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Diagnosis of polio? |
Polio virus can be detected in specimens from the throat, feces and occasionally cerebrospinal fluid |
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What vaccines are available for poliovirus? |
Inactivated polio vaccine (IPV) Live attenuated oral polio vaccine (OPV) |
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What polio vaccine allows for indirect immunization? |
Live attenuated oral polio vaccine |
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What families of viruses are associated with gastroenteritis? |
Reoviruses Caliciviruses Astroviruses Enteric viruses |
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What viruses are family Reoviridae? |
Rotavirus Orthoreovirus |
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What viruses are in the Calciviridae? |
Norovirus Sapovirus |
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What are reoviruses ? |
A diverse group of respiratory enteric orphan viruses that infect a variety of hosts |
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Rotavirus structure |
Icosahedral, non-enveloped virus that has a double layered capsid |
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What is the outer capsid of rotavirus composed of? |
Structural proteins |
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Proteolytic cleavage of outer capsid in rotavirus does what? |
Activates the virus for infection |
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What are reovirus core proteins? |
5' methyl guanosine mRNA capping enzyme RNA dependent RNA polymerase |
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What are sigma1 and vp4 ? |
Capsid spike proteins in reovirus and rotavirus |
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What are sigma3 and Vp7 |
Viral attachment proteins present within the capsid of reovirus and rotavirus |
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Reovirus genome is composed of |
10 dsRNA segments |
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Rotavirus genome is composed of |
11 dsRNA segments |
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Reovirus genome segments fall into what classes? |
Lambda Micro Sigma |
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What is Baltimore class 3? |
DsRNA Viruses |
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Example of a class 3 virus |
Rotavirus |
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What are coliform bacteria? |
Organisms that are present in the environment and in the faeces of warm-blooded animals |
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What is an orphan virus? |
A virus that is not associated with a disease but may possess pathogenicity |
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Where does rotavirus replication occur? |
Columnar epithelial cells of the small intestine |
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Immunity to rotavirus requires |
IgA in the gut lumen |
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What outer capisd proteins are normally used for rotavirus serotyping |
Vp4 and vp7 |
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What illness does rotavirus cause ? |
Rotavirus is a highly infectious stomach bug that typically affects babies and young children |
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How is rotavirus transmitted |
Faecal oral route |