Virulence factor regulation

Question 1

Location of virulence genes

Answer 1

On virulence plasmids or chromosomal location.
Can change location > mobile elements.
Pathogenicity islands.

Question 2

Pathogenicity islands

Answer 2

Genomic regions with high densitiy of VFs. Contain multiple virulence genes.
Often flanked by direct repeats, tRNAs, insertion sequence elements. Presence of (non-funcitonal) mobility genes.
GC content characterisitc > id. Derived by horizontal gene transfer.

Question 3

Types of gene regulation

Answer 3

1. Transcriptional regulation
2. translational regulation
3. post-translational regulation

Question 4

Types of transcripitional regulation

Answer 4

1. Coordinated gene expression by sigma factors
   (determine promoter specificity of RNA pol, allow simultaneous regulation of many genes)
2. transcriptional activators and repressors (TFs, local or global regulators)

Question 5

Sigma factors

Answer 5

Forms RNA pol holoenzyme with the 4 core subunits.
More varied environment > more sigma factors.
Compettion for core RNA pol > regulation of virulence genes.
E coli: RpoS

Question 6

Listeria monocytogenes VF regulation

Answer 6

Global regulator: PrfA (Pathogenic Listeria strains.
Necessary for switch from extracellular for intracellular
Activated in host: mRNA is thermosensor.)
VF: phospholipases, ActA protein

Question 7

S. aureus - VF regulation

Answer 7

Timing of VF expression to promote adherence/inhibit immune sytem/damage host/allow spread.

Switch mediated by RNAIII: bifunctional, encodes hemolysin but also acts as regulator

Question 8

Coupling of sensory systems to gene regulation

Answer 8

1. Sensor and regulator in one protein

2. Sensor and regulator separated (two-component regulatory systems)

Question 9

Sensor/regulator in one protein - example

Answer 9

DtcR (repressor of diphteria toxin gene)

- senses Fe2+ > toxin is only expressed inside host (low)