5, spread to other sites
1, invade into host cells and their circulatory system
2, disrupt host cells to gain deeper tissue access
3, miscellaneous mechanisms - fribinolysis and actin-mediated locamotion
S. aureus spreading via Staphylokinase
- it complexes with plasminogen to activates plasmin proteolytic activity
- this causes the breakdown of fibrin clots - helps in bacetria spreading
ActA is a direct homologue of a host protein involved in actin polymerisation. The bacteria have adapted a host cell protein via horizontal acquisition to manipulate cellular functions.
- profilin - actin binding protein
- Arp2/3 complex - initiates of ew filaments
- VASP - actin filament elongation
- Actin monomers
ActA located on the surface is responsible for polymerisation of actin at the bacterial surface. The polarisation of ActA gives polarity in bacetrial division. It is trapped at 'old' pole where peptidoglycan turnover is slow.
During division, new membrane is needed therefore old migrate to poles to make way for the new.
6, tissue damage
- access to nutrients
- transmission to new sites
- target immune cells
- cell death can initiates immune response
There are two types of toxin:
Exotoxins - soluable and actively secreted
Endotoxins - natural products released only after bacterial lysis
Exotoxins give rise to virulence factor. It could damage the host by destroying cell and disrupting cellular metabolism.
Type I exotoxins
- act from the extracellular cell surface
- bind to receptor on the surface and stimulates intracellular signalling pathways
Type II exotoxins
- designed primary to disrupt the cellular membrane - channel-forming toxins
- it may be clel type specific or non specific
Type III exotoxins
- intercellular toxins that gain access to cytoplasm in order to exert effects
Inject toxins from bacterial to target cell cytosol - E.g. T3SS, T4SS, T6SS
A-B or A-B5 intracellular toxins
ADP-ribosyl group is transfered from NAD to a side chain of a host cell target protein by ADP-ribosyltransferase.
A-B5 toxin prevents inactiviations of mammalian adenyl cyclase which results in excess cAMP.
Zinc-dependent metalloproteases. It cleaves neurospecific proteins.
E.g. Bordetella pertussis. A G-protein deamiddases which can polymerise as well as depolymerise
Can cleave DNA, rRNA and inhibit protein synthesis
Type IV exotoxins
- Damage the extracellular matrix to enhance bacterial spread to deeper tissue
Hyaluronidase and collagenase - breaks the bnd beween proteins that form connective tissue
B.pertussis tracheal toxin
- It's a peptidoglycan monomer - can breakdown products during bacterial division
- This triggers a violent coughing episodes
Mycobacterium ulcerans mycolactone toxins
- Derived from polyketide necrotizing exotoxin with pro-apoptotic and anti-inflammatory activities
- devastates the skin lesions - abnormalities of an organisms tissue
Contain pathogen associated molecular patterns - PMAPs - recognised by pattern recognitions receptors - PRRs: Extracellular - TLRs; Intracellular - NLRs (nod-like receptors).
They are largely responsible for dramatic clinical manifestations of abcetrial infections.
Addaptation of pathogenic bacetria to new environments
- this is done through QS
- S. aureus process species specific QS system called Agr - it is expressed the most in stationary phase when cell density is high.
Autoactivation of agr locus
Production of AgrD propeptides is matured by proteolytic digestion before being secreted into excellular environment. The secretion is carried by anchored membrane protein AgrB. When cell density is high, autoinducer peptide level is also high. (QS effect). The level of ArgB is sensed by AgrC - a sesor kinase. The phosphate residue is relay back to AgrA - the P~AgrA activates transcription from P2 and P3 promoters.
Regulation by RNAIII
This may be done by targeting DNA promoters to create binding sites for additional regulatory proteins and to provide access of Shine-Dalgarno seqeunce of binding by Ribosomes.
May target activity of proteins.
Regulation by small RNAs in bacteria
Regulates both transcription and post-transcriptional effects.
bvgAS locus is a tranmembrane sensor kinase and a DNA-binding response regulator. It response to environment signals (Temperature and MgSO4 level) to become autophosphorylated - relayed onto bvgA to bind to DNA to activates vags (virulence activated genes) and turn off vrgs (virulence repressed genes).
Causes the pathogen to alternates between environment reservior, insect vector and mammalian host - used by bacetria to sense their environment and control virulence gene expressio.
Involved prfA - post transcriptionally regulated. The RNA secondary structure in the UTR of prfA senses temperature - DNA topology bends or supercoil DNA according to the temperature.
Sensing the target cell environment
Through cell receptor or iron concentrations.
The two T3SS are never expressed at the same time or place (temporal or spatial). the bacteria can sence their surroundings and change their spatial and temporal gene expression patterns.
Low Ca response trigger T3S by Yersinia spp.