Microbes and disease

 Significant advances in medical microbiology

  Human microbiome
 Concept first suggested by Joshua ledberg
 Microbiome- the ecological community of commensal symbiotic and pathogenic
microorganisms that literally share our body space
 Ledberg and McCra 2001
 Us funded project 250 volunteers
 Microbiome shield body tissues against invasion
 Production of vitamins by bacteria
 Implicated in range of conditions
 Obesity
 Type 1 diabetes
 Crohns disease
 Irritable bowel syndrome
 Colon cancer
 Emerging field of research
 Major implications
 Use of probiotics and prebiotics
 Effects of antibiotic (mis)use

Virulence factors
 Virulence factors determined by many factors
 Adhesion
 Antiphagocytic activity
 Production of toxins
 Conventional virulence factors
 Bacterial toxins
 Adhesions
 Cell surface carbohydrates and capsules
 Secreted hydrolytic enzymes
 Lps
 Other factors
 Secretion machineries
 Siderophores
 Catalases
 Genetic regulators
 Genetic elements encoding virulence factors
 Virulence may be plasmid or phage encoded
 Plasmid encoded coagulase, haemolysis and enterotoxin of s aureus
 Phage encoded dphteria toxin of Corynebacterium diphtheriae
 In chromosome may occur in clustered pathogenicity islands
 Listeria pathogenicity island 1
 Encodes 6 gene products essential for life
 Some genetic elements are the result of horizontal gene transfer
 Other genetic elements can aid in horizontal gene transfer
 MRSA
 Methicillin resistant staphylococcus aureus
  Great concern
 Limited antibiotic treatment
 Last antibiotic vancomycin
 Now VRSA isolates have been oslated
 Emerging pathogens
 New pathogens
 Includes bacteria with wide environmental distribution
 Opportunistic pathogens dangerous in hospitals
 Burkholderia cepacian
 Versatile species
 Associated with plants and soil
 Able to degrade complex aromatic pollutants
 In mid 190s recognized in CF patients
 Can cause cepacian syndrome in 10% of CF patients
 Patient to patient transmission

Antibiotics and antimicrobial resistance

 Antibioitcs usef for 100 years
 Moldy bread in egybt
 First modern antiobiotic 1909
 Arsenic based treatment for syphilis
 First antibiotic from a natural source
 Penicillin 1928
 5 major types of antiobitcs
 Beta lactams
 Macrolides
 Fluoroquinolones
 Tetracclines
 Aminoglycosides
 Bacteria that are resistant to all antibiotics
 Reduced permeability
 Inactivation
 Target alteration
 New resistance pathway
 Efflux
 Resistance can arise very quickly
 Soltions
 New drugs
 New targets
 Ie cell wall, prtoeins
 Drug combinations and augmentative compounds

Bacterial vaccination
 Using an infectious agent to raise immunity to that agent
 Evidence of variolation in china over 1000 years ago
 Using old small pox pustules to cause mild disease in others
 1796 edward jenner invents vaccine
 Infecting someone with cowpox would prevent someone from getting small pox
 1879 louis Pasteur found pasteruella multocida (chicken cholera)
 Became much less virulent after exposure to air for a long period
 Old culture infected chicken did not cause disease (immunity)
 Deduced this was vaccination
 Difference was a weakened pathogen (attenuated)
 1881 testd weakend anthrax on sheep
 No vaccinated sheep died when exposed
 First proof that attenuation vaccination worked
 C. Tetani neurotoxin leads ot over activity of motor neurones causing muscle spasms
(lockjaw)
 Toxin based infection
 Vaccine targets toxin
 Tenospasmin
 Plasmid encoded 150kDa protein
 Ab toxin
 Neturotix (lethal)
 Excond most toxic compound known
 Release cell lysis spreading though blood and lymph
 Targets CNS and binds to peripheral nerve terminals
 Halts the release of glycine and GABA neurotransmitters
 Recovery form tetanus does not confer immunity
 Lethal dose too small to raise immunity
 Horse antitoxin bodies used in first world war
 Now use formalin inactivate dtoxin
 100% protection for 10 years
 No real herd immunity
 Meningitis
 Infalmation of the protective membranes that cover the brains and spinal cord
 Many different causes
 Viruses
 Bacteria
 Fungi
 Protozoa
 Acute bacterial meningitis is a life threatening infection
 75% of cases caused by
 Haemophilus influenzae
 Streptococcus pneumoniae
 Nesseria meningitidis
 Importance virulence determinants include polysaccharide capsules, a key
component of vaccines
 Haemophilus influenze
 Gram negative coccobacillus
 Non-encapsualted strains carried asymptomatically in urinary tract
 Six stereotypes a-f (distuinguished by capsular pollysacharide
 Sterotybe b (his) causes 90% of invasive infections
 Treatment with ampcilin or chloramphenicol
 Major cause of bacterial meningitis
 Hib vaccine
 Conjugated vaccines
 Peptide carrier to ensure immune respons
 Three conjugated hib vavvines in 1992
 HbOC
 PRP-T
 PRP-OMP
 All exhibit more then 90% proactive efficacy
 Near elimination of disease
 Cost often too high for developing countries