What types of pathogen can be used as a vaccine?
- Dead pathogen
- Attenuated pathogen
- Only the antigenic components of the bacteria
What are possible antigenic vaccine targets?
- Outer membrane proteins
- Fimbriae
- Virulence factors
- O-antigen
- Capsule
How many serogroups does Niesseria meningitidis have?
5
Why has it been difficult to develop a vaccine for the five serogroup?
Serogroup B capsule has polysialic acid
Diffiult to target becuase also present on host cells - so there is a risk of autoimmunity
What is the easiest way to check if protein is a membrane protein?
PResence of a signal sequence
How was a vaccine developed for this serogroup?
Reverse Vaccinology
What are the two types of antibiotic?
Bacteriocidal - kills the bacteria outright
Bacteriostatic - stops bacterial growth
What are the 3 main targets of current successful antibiotics?
- Cell wall synthesis
- Ribosomes
- DNA topoisomerase
What two types of antibiotic interfere with peptidoglycan synthesis?
- Gylcopeptides - prevent incorporation of new subunits
- Beta-lactams - Inhibit enzymes required for transpeptidation
What is MIC?
Minimum inhibitory concentration
What are the antibiotic resistance mechanisms?
- Modify the antibiotic target
- Limit antibiotic in the cell
- Reduce entry
- Increase efflux
- Bypass the pathway
- Enzymatic inactivation of the antibiotic
What resistance mechanism exist aginst beta-lactams?
Produce and secrte beta-lactamases
Alter the PBP so the antibiotic cannot interact with it
What resistance mechanisms exist against vancomycin?
Intrinsic resistance of Gr- bacteria
Alter target
How can a strain acquire resistance?
- Horizontal gene transfer
- Mutation in target or regulatory elements
What target has been used to treat E.coli infection?
Fimbriae - FimH and FimA
What other target was found by Greene?
Type 1 using a pilicide
What treatment has started be used for antibiotic related diarrhoea
Replacement microbiome
Stope uncontrolled growth by clostridium difficile
How does antibiotic treatment lead to C.difficile toxin production?
- Antibiotic treatment will stop primary bile salt to secondary bile salt transition
- Secondary bile salts can no longer inhibit vegetative growth and hence the toxin can be produced
What are the model systems for human bacterial pathogenesis?
- Primates
- Mouse
- Cell lines
- Drosophila
- C. elegans
- Zebrafish
- Plants
- Computational models
What are the stages of clincial trails?
- Lab studies
- Phase 1 - human safety in tens of patients
- Phase 2 -Expanded safety in hundreds of patients
- Phase 3 - Efficacy and safety in thousands of patients
