Bacterial Infections

Question 1

Community-acquired infections: define an outbreak of infectious disease and explain how outbreaks are identified; list bacterial pathogens that cause community-acquired infection, explain the routes and types of infection caused, and list important bacterial virulence factors

List important bacterial virulence factors

Explain the routes and types of infection caused by these bacterial pathogens

Answer 1

• Diverse secretion systems.
• Flagella – for movement, attachment.
• Pili – adherence.
• Capsule – protect against phagocytosis.
  
  • Streptococcus pneumoniae**.
• Endospores – metabolically dormant forms of bacteria that can resist heat.
  
  • Bacillus sp**. And Clostridium sp.
• Biofilms – (communities of bacteria) aggregates of bacteria embedded in polysaccharide matrix – develop antibiotic resistant.
  
  • Pseudomonas aeruginosa and Staphylococcus epidermidis.

Bacteria release proteins - called exotoxins

• Exotoxins – toxins that damage biological systems:
  
  • Neurotoxins – act on nerves or motor-end-plates.
    
    • Tetanus or Botulinum toxins.
  • Enterotoxins – act on GIT:
    
    • Infectious diarrhoea – Vibrio cholera, E. coli, Shigella dysenteriae, Campylobacter jejuni.
    • Food poisoning – Bacillus cereus, Staph. aureus.
  • Pyrogenic exotoxins – stimulate release of cytokines:
    
    • Staph. aureus or Strep. pyogenes.
  • Tissue invasive exotoxins – enzymes that allow bacteria to tunnel through tissue:
    
    • Staph. aureus**, Strep. pyogenes, Clostridium perfringens.
  • Misc. exotoxins – specific to certain bacteria, function not well understood:
    
    • Bacillus anthracis**, Corynebacterium diphtheriae.
• Endotoxins – i.e. Lipid A in LPS from gram- bacteria.
  
  • Only produced by gram –ve bacteria - outer membrane (lipopolysaccharide molecules).
  • NOT a protein – a lipid A moiety of LPS.
    
    • Shed in steady amounts from living bacteria.
  • When treating a patient with a gram-ve infection, the ABs can make them worse:
    
    • Bacteria lyses à release large quantities of LPS/endotoxins à septic shock.

Question 2

Define an outbreak of infectious disease

Answer 2

Outbreaks

• Outbreak – a greater than normal or greater than expected increase in incidence of a disease with a particular infection in a given period of time or place or both.
• Identification of an outbreak:
  
  • Surveillance.
  • Good and timely reporting systems.
  • PCR.

example:

• Haemolytic-uraemic syndrome – triad of acute renal failure, haemolytic anaemia and thrombocytopenia.
  
  • Caused by EHEC – enterohaemorrhagic E. coli.
    
    • Reservoir is usually in cattle.
• The outbreak was the result of a fusion the EHEC and the EAHC strains to form the EAHEC strain.
  
  • EHEC – Enterohaemorrhagic E. coli.
  • EAEC – Enteroaggregative E. coli.
  • EAHEC – Entero-aggregative-haemorrhagic E. coli.

How Outbreaks are Identified:

• Possible epidemic case:
  
  • Any person that has developed the symptoms AND has met a laboratory criteria (e.g. isolation of agent).
• Probable epidemic case:
  
  • Any person that has met the above criteria AND has been in epidemic country, consumed possibly contaminated food, been in close contact with a confirmed epidemic case.
• Confirmed epidemic case:
  
  • Any person meeting criteria for a possible case AND has had strain isolated.

Question 3

Describe the use of PCR to identify an outbreak

Answer 3

The PCR showed that the isolate contained aspects of both EHEC and EAEC:

• EAEC – 2 plasmids:
  
  • pAA-type plasmids – contain aggregative adhesion fimbrial operon.
  • ESBL plasmids – gene encoding for extended-spectrum beta-lactamases.
• EHEC – prophage – encoding the Shiga toxin – characteristic for EHEC strains.

Shiga/Vero Toxin (Stx2):

• Shiga toxins have an AB5 subunit composition.
  
  • StxA is the enzymatic portion – cleaves RNA -> inhibition of protein synthesis and might affect gut commensal bacteria as well.
  • StxB is the pentamer that binds to host cell receptors.
• Shiga toxins are encoded on bacteriophages and contribute to horizontal gene transfer meaning they can be given to other bacteria types in phages.
• EAEC can colonize the larger and small bowel à affects gut flora.
• EAECs virulence factor – Aggregative Adherence Fimbriae (AAF):
  
  • AFF required for adhesion to enterocytes and stimulates IL-8 response.
  • AFF also allows a biofilm formation.

Question 4

List bacterial pathogens that cause community-acquired diseases in Europe

Answer 4

1. Respiratory tract infections
2. Sexually-transmitted Infections (STIs)
3. Food- and waterborne diseases and zoonoses
4. Emerging and vector-borne diseases
5. Vaccine-preventable diseases
6. Antimicrobial resistance and HCA infections – covered in next lecture.

Question 5

Respiratory tract infections

Answer 5

1. Legionnaire’s disease – Legionella pneumophilia (gram-ve):
   
   1. Location – lives in amoeba in – ponds, lakes, air conditioning.
   2. Route of infection (RoI) – inhalation of contaminated aerosols.
      
      1. Grows in alveolar macrophages.
   3. Virulence factor – type IV secretion systems – (allows bacteria to inject toxic proteins to the outside) legionella replicates in legionella containing vacuoles (LCVs) inside cells.
2. Tuberculosis – Mycobacterium tuberculosis (gram+ve):
   
   1. Virulence factor – has an extra lipid layer & can enter a dormant state for reactivation.
   2. 77% success of first treatment and 54% success of second treatment – has MDR.

Question 6

Sexually-transmitted Infections (STIs):

Answer 6

1. Chlamydia – Chlamydia trachomatis (gram-ve obligate intracellular parasite):
   
   1. Most common STI in Europe and causes >3% of the world’s blindness.
2. Gonorrhoea – Neisseria gonorrhoeae (gram-ve):
   
   1. Urogenital tract infection infecting non-ciliated epithelial cells.
   2. Virulence factors – pili, antigenic variation mechanisms.

Question 7

Food- and waterborne diseases and zoonoses:

Answer 7

1. Campylobacteriosis – Campylobacter sp. (mostly C. jejuni):
   
   1. Most infectious GI disease in the EU with small (0-4) children in the highest risk group.
   2. Infection route via uncooked poultry but does not cause outbreaks.
   3. Virulence factors – adhesion, invasion factors, flagella motility, T4 secretion systems, toxins.
2. Salmonellosis – Salmonella sp. (gram-ve):
   
   1. Common GI infector from undercooked poultry but causes outbreaks.
   2. Highest risk in small children (0-4).
   3. Virulence factors – T3 secretion systems encoded on pathogenicity islands.
      
      1. SPI1 for invasion, SPI2 for intracellular accumulation.
3. Cholera – Vibrio cholera (gram-ve):
   
   1. Acute severe diarrhoeal disease.
   2. Virulence factors – T4 fimbria, cholera toxin (increased cAMP -> opening of (CFTR) Cl^- channels and expulsion of water from cells), carried on phages.
4. Listeriosis – Listeria monocytogenes (gram+ve):
   
   1. Risk groups of immunocompromised and pregnant people (no unpasteurised cheese)
   2. Virulence factors – actin-based cell mobility.

Question 8

Emerging and vector-borne diseases and vaccine-preventable diseases

Answer 8

Emerging and vector-borne diseases:

1. Plague – Yersina pestis (gram-ve).
2. Q fever – Coxiella burnetti (gram-ve).
3. Smallpox (A VIRUS) – eradicated.

Vaccine-preventable diseases:

1. Diphtheria – Clostridium diphtheriae (gram+ve).
2. Invasive HA disease – Haemophilus influenzae (gram-ve).
3. Invasive meningococcal disease – Neisseria meningitides (gram-ve).
4. Invasive pneumococcal disease – Streptococcus pneumoniae (gram+ve)
5. Pertussis – Bordetella pertussis (gram-ve).
6. Tetanus – Clostridium tetani (gram+ve).

Note; mass vaccination reduced by >97% the incidence of 9 infectious diseases and eliminated 2 of them (poliomyelitis and smallpox).

Antimicrobial resistance and HCA infections – covered in next lecture.

Question 9

Hospital acquired infections: explain why hospital patients are particularly at risk, list examples of common hospital acquired infections and explain routes and types of infection caused

Question 10

Explain why patients in hospital are particularly at risk

Answer 10

• Definitions:
  
  • Antimicrobial – interferes with growth & reproduction of a ‘microbe’.
  • Antibacterial – describes agents that reduce or eliminate harmful bacteria
    
    • Antibiotics are a type of antimicrobial.
• Hospital-Acquired Infections:
  
  • 1 in 18 patients acquires a HAI – 3.2m a year get an HAI, 37,000 of those die of them.
  • Most frequent HAIs – surgical site infections, UTIs, pneumonia, bacteraemias, GI infections.
  • HAIs cost an ~£1b extra a year.

Causes of HAIs

1. Interventions – catheters, intubation, chemotherapy, prosthetics, lines, prophylactic antibiotics and inappropriate prescribing.
2. Dissemination – carriers of the infection from person to person.
3. Concentration.

Question 11

List examples of common bacterial common infections

Answer 11

Question 12

Explain the problem of antibiotic resistance and give examples

Answer 12

Pathogenic E. coli

• Most frequent cause of bacteraemia by a gram-ve bacteria.
• Most frequent cause of community and HAI UTIs.
• Pathogenic E. coli
• Increase in MDR-strains of E. coli.

Resistances:

• 3rdGen cephalosporin resistance (20% in some countries) (b lactam ABs they attack enzymes necessary for the sysnthesis of the peptidoglycans bind to penicillin binding proteins and inhibit them)
• most resistance is mediated by the ESBLs: Extended-spectrum b lactamase
• Still sensitive to Carbapenems
• Carbapenemase enzyme

Klebsiella pneumoniae

• Causes – UTIs and respiratory tract infections.
• Risk groups – immunocompromised.
• Resistances:
  
  • 3^rdGen cephalosporins, fluoroquinolones and aminoglycosides.
  • CRKP – Carbapenem-Resistant Klebsiella pneumoniae – species of CRE most commonly encountered in the united states.

Pseudomonas aeruginosa

• Risk groups – immunocompromised.
• Resistances:
  
  • High proportions of strains are resistant to several antimicrobials.
  • Carbapenem resistance is above 10% in half EU countries.

MRSA

• Most important cause of antimicrobial resistant infection worldwide.
• MRSA expresses an additional penicillin binding protein (PBP2A) which has a low affinity for methicillin (b- lactam) and can therefore function.

MRSA strains can therefore still synthesise peptidoglycans

VRE

• 3^rd most frequently identified cause of nosocomial blood stream infections (BSIs) identified in the US.
• Resistance:
  
  • Vancomycin resistance is around 60%.
• Pathway – VRE synthesises a different peptidoglycan precursor that is not targeted by the vancomycin.