Virulence I Flashcards
Define virulence factor. List examples.
bacterial property required for entry, growth, and survival in host
- capsule to resist complement killing
- adhesins to adhere to host
- factors to adapt to acidic environments
- enzymes to synthesize necessary nutrients not provided by host
Define virulence gene.
gene that encodes virulence factor; if lost (mutation, loss of plasmid), decreases virulence
- often located on mobile elements (transposons, plasmids)
- located in pathogenicity islands
Define pathogenicity island.
- large localized regions of the chromosome containing virulence genes
- absent in closely related non-pathogenic strains
Describe the organization of a typical operon.
promoter - operator - cistrons - terminator
- operon is multicistronic transcription unit
- encodes multicistronic mRNA
Describe the process of transcription.
- sigma unit of the RNA Polymerase (RNAP) recognizes and binds to the promoter
=> forms closed complex: sigma-RNAP-DNA connection - once bound, RNAP opens up the DNA => open complex
- strand separation allows for mRNA transcription complementary to sense strand
- mRNA elongation continues until RNAP hits the terminator sequences
Describe the regulation of transcription initiation.
- determines initiation by setting frequency
- depends on affinity for RNAP for DNA
- via repressors, activators, and inducers
Define regulon. Outline the steps involved in utilizing this global control system.
- group of operons subject to control by a common regulator
GLOBAL CONTROL SYSTEM
1. sensor molecule => cell sense stimulus
2. sensor signals activation/deactivation of regulator
3. regulator binds to several operons
4. turn some on, some off
5. gene products respond to original stimulus
6. gene products exert control on their own expression
List 4 stressors an intestinal pathogen must survive to cause disease.
- higher temperature
- higher osmolarity
- low pH in stomach
- high pH, bile, lack of oxygen, and organic nutrients in intestine
- limited iron availability (siderophores!!!)
Define cistron.
- structural gene that encodes a polypeptide
- located on the multicistronic operon
Define core enzyme. Define holoenzyme.
core enzyme = alpha, alpha, B, B’
- homologous to all RNAP
holoenzyme = core + sigma
Define CRP.
- dimer
- when bound to cAMP => binds to DNA
=> interacts with alpha-CTD => closed complex
Under what conditions do intestinal pathogens typically reside in before ingestion?
- low temperatures
- low ionic strength
- neutral pH
- low concentration of organic nutrients
What genes do intestinal pathogens need to express to survive intestinal environment?
- iron chelators to scavenge for iron
- proteins that permit it to tolerate low gastric pH
- flagella and chemotaxis to allow migration into suitable niche
- adhesins to colonize intestine
- toxins and invasins to elicit disease
- virulence genes must be turned on, other genes must be turned off
Compare and contrast repressors, inducers, and activators.
REPRESSORS
- binds operator at a site overlapping the promoter
- prohibits binding of RNAP
- steric hindrance
INDUCER
- small molecule that binds the repressor
- causes dissociation of repressor from DNA via conformational change
- no longer represses => normal transcription levels
ACTIVATORS
- interacts with RNAP
- increases ability of RNAP to bind to DNA
Describe the role of the sigma complex in transcription initiation.
- binds to promoter (typically, TTGACA or TATAAT
- involved in closed and open complex
- homologs in archaea and eukarya
- homologs bind TATA (eukaryotic promoter)
