2. Community and Hospital acquired bacterial infections Flashcards

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1
Q

Define virulence factor.

A

Molecules produced by pathogens that contribute to the pathogenicity of the organism

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2
Q

List some common bacterial virulence factors and include their function.

A
  • - Flagella – movement and attachment
  • - Pili – adherence factors
  • - Capsule – protects against phagocytosis
  • - Endospores – metabolically dormant forms of bacteria – they are heat, cold, desiccation and chemical resistant
  • - Biofilms – organised aggregates of bacteria embedded in a polysaccharide matrix – antibiotic resistant
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3
Q

Give examples of bacteria that possess the following virulence factors:

a. Capsule
b. Endospores
c. Biofilms

A

a. Capsule - S. pneumoniae

b. Endospores - Bacillus sp. and Clostridium sp.

c. Biofilms - P. aeruginosa and S. epidermidis

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4
Q

What are exotoxins?

A

A toxin released by a living bacterial cell into its surrounding

  • toxins that damage biological systems
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5
Q

What are the different types of exotoxin?

Give examples of bacteria that produce such toxins.

A
  • - 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.
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6
Q

List FIVE different bacterial virulence factors and an example of a bacterium for each

A
  • - Capsule - S.pneumoniae
  • - Endospores - clostridium, bacillus
  • - Biofilms - pseudomonas aeruginosa, staphylococcus epidermis
  • - Neurotoxins - tetanus, botulinum
  • - Enterotoxins - infectious diarrhoea (V. cholera, E. coli, C. Jejuni, etc …), food poisoning (S. aureus, B. cereus)
  • - Pyrogenic exotoxins - S. Aureus, S. pyogenes
  • - Tissue invasive exotoxins - S. Aureus, S. pyogenes, C. perfringens
  • - Endotoxins - any gram negative bacteria
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7
Q

What is an endotoxin?

A

This is the lipid A part of lipopolysaccharide that is found on the outer membrane of Gram-negative cells

  • NOTE: so ONLY Gram-negative cells can produce endotoxins*
  • NOT a protein – a lipid A moiety of LPS - shed in steady amounts from living bacteria.*
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8
Q

Why can treating patients with Gram-negative infection sometimes worsen their condition?

A
  • Antibiotics can cause lysis of the bacteria meaning that the endotoxins/LPS are released into the circulation in large quantities
  • This can trigger an immune response that leads to SEPTIC SHOCK
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9
Q

What is an outbreak and how can it be identified?

A

Outbreak: a greater than normal or greater than expected number of individuals infected or diagnosed with a particular infection in a given time period, or a particular place, or both

Identified using:

  • Surveillance
  • Good and timely reporting systems are necessary
  • PCR
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10
Q

What was the 2011 E. coli outbreak in Germany caused by?

What were the symptoms of infection by this bacterium?

What was special about the bacterial strain that caused by outbreak?

A

Caused by: Enteroaggregative shiga toxin producing E. coli O104:H4 strain

Symptoms:

  • Gastroenteritis
  • Haemolytic uraemia syndrome (acute renal failure + haemolytic anaemia + thrombocytopenia)

Bacterial stain:

  • The bacterial strain was an enteroaggregative E. coli strain (EAEC) that had acquired the ability to produce shiga toxin (through phagetransfer)
  • Shiga toxin production is a feature of Enterohaemorrhagic E. coli (EHEC)
  • This produced a new strain called Enteroaggregative haemorrhagic E. coli (EAHEC)
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11
Q

Describe the structure of shiga toxin.

Describe the action of shiga toxin.

A

Structure: There is an A subunit that is non-covalently associated with a pentamer of protein B

Action:

  • Subunit A is the enzymatically active domain
  • Subunit B is responsible for binding to the host cell membrane
  • Subunit A cleaves 28S ribosomal RNA in eukaryotic cells thus inhibiting protein synthesis
  • Bacterial ribosomes are also a substrate for subunit A so it can lead to decreased proliferation of susceptible bacteria (e.g. commensal microflora of the gut)
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12
Q

How was the shiga toxin gene transferred between bacteria?

A

Bacteriophage

Shiga toxins are encoded on bacteriophages and contribute to horizontal gene transfer meaning they can be given to other bacteria types in phages.

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13
Q

What is the important virulence factor in EAEC?

A

EAEC can colonise the larger and small bowel → 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.
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14
Q

Give examples of respiratory tract infections - the bacteria they are caused by and their virulence factors

A

a. Legionnaire’s disease – Legionella pneumophilia (gram-ve):

  • i. Location – lives in amoeba in – ponds, lakes, air conditioning.
  • ii. Route of infection (RoI) – inhalation of aerosols.
      1. Grows in alveolar macrophages.
  • iii. Virulence factor – type IV secretion systems – legionella replicates in legionella containing vacuoles (LCVs) inside cells.

b. Tuberculosis – Mycobacterium tuberculosis (gram+ve):

  • i. Virulence factor – has an extra lipid layer & can enter a dormant state for reactivation.
  • ii. 77% success of first treatment and 54% success of second treatment – has MDR.
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15
Q

What feature of Mycobacterium tuberculosis makes it more difficult to treat?

A

It has a mycolic acid outer membrane – this prevents normal antibiotics from getting into the cell

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16
Q

Give examples of sexually transmitted infections (STIs) - the bacteria they are caused by and their virulence factors

A

a. Chlamydia – Chlamydia trachomatis (gram-ve obligate intracellular parasite):

  • i. Most common STI in Europe and causes >3% of the world’s blindness (due to eye infection)

b. Gonorrhoea – Neisseria gonorrhoeae (gram-ve):

  • i. Urogenital tract infection infecting non-ciliated epithelial cells.
  • ii. Virulence factors – pili, antigenic variation mechanisms.
17
Q

Give examples of food and waterborne diseases and zoonoses

  • the bacteria they are caused by and their virulence factors
A

a. Campylobacteriosis – Campylobacter sp. (mostly C. jejuni):

  • i. Most infectious GI disease in the EU with small (0-4) children in the highest risk group.
  • ii. Infection route via uncooked poultry but does not cause outbreaks.
  • iii. Virulence factors – adhesion, invasion factors, flagella motility, T4 secretion systems, toxins.

b. Salmonellosis – Salmonella sp. (gram-ve):

  • i. Common GI infector from undercooked poultry but causes outbreaks.
  • ii. Highest risk in small children (0-4).
  • iii. Virulence factors – T3 secretion systems encoded on pathogenicity islands.
      1. SPI1 for invasion, SPI2 for intracellular accumulation.

c. Cholera – Vibrio cholera (gram-ve):

  • i. Acute severe diarrhoeal disease.
  • ii. Virulence factors – T4 fimbria, cholera toxin (increased cAMP → opening of Cl- channels and expulsion of water from cells), carried on phages.

d. Listeriosis – Listeria monocytogenes (gram+ve):

  • i. Risk groups of immunocompromised and pregnant people.
  • ii. Virulence factors – actin-based cell mobility.
18
Q

Explain how cholera toxin works.

A
  • It has A and B subunits
  • A is the active toxin
  • B allows entry of the toxin into the epithelial cell
  • The A subunit activates adenylate cyclase, thus increasing the production of cAMP
  • The cAMP then binds to CFTR and causes Cl- efflux
  • Water follows the ion movement so you get massive movement of water into the lumen of the intestine
19
Q

What are some special features of Listeria?

A

They can enter non-phagocytic cells and cross tight barriers (e.g. BBB and maternal-foetal barrier)

20
Q

What are emerging and vector-borne diseases?

A

a. Plague – Yersina pestis (gram-ve).

b. Q fever – Coxiella burnetti (gram-ve).

c. Smallpox (A VIRUS) – eradicated.

21
Q

List some vaccine-preventable diseases. Identify which are viral.

A
  • a. Diphtheria – Clostridium diphtheriae (gram+ve).
  • b. Invasive HA disease – Haemophilus influenzae (gram-ve).
  • c. Invasive meningococcal disease – Neisseria meningitides (gram-ve).
  • d. Invasive pneumococcal disease – Streptococcus pneumoniae (gram+ve)
  • e. Pertussis – Bordetella pertussis (gram-ve).
  • f. Tetanus – Clostridium tetani (gram+ve).

  • Measles *, Mumps*, Rubella*, Polio**
  • Rabies*
22
Q

Define the following:

a. Antimicrobial
b. Antibacterial
c. Antibiotic

A

a. Antimicrobial - interferes with the growth and reproduction of a microbe

b. Antibacterial - commonly used to describe agents that reduce or eliminate harmful bacteria

c. Antibiotic - a type of antimicrobial that is used as medicine for humans and animals

23
Q

What is a hospital-acquired infection? Give examples

Why do they cost money to the healthcare system?

A

- HAI: Infections that occur after exposure to healthcare Infection starts >48 hours after admission to hospital

  • They increase the length of stay at hospital (cost about £1bn extra a year

Most frequent HAIs – surgical site infections, UTIs, pneumonia, bacteraemias, GI infections.

24
Q

List some medical interventions and other factors that can increase the risk of infection.

A

Medical interventions:

  • Catheterisation
  • Intubation
  • Lines (e.g. central venous lines)
  • Chemotherapy, prophylactic antibiotics, inappropriate prescribing
  • Prosthetic material

Other:

  • Dissemination by healthcare staff (carriers of infection from person to person)
  • Concentration of ill patients
25
Q

What are the ESCAPE pathogens and what is the main problem with them?

A

These are all antibiotic resistant

  • - Enterococcus faecium (+ve) → vancomycin resistant
  • - Staphylococcus aureus (+ve) → MRSA
  • - Clostridium difficile (+ve) → can infect due to previous AB treatment
  • - Acinetobacter baumanii (-ve) → highly drug resistant
  • - Pseudomonas aeruginosa (-ve) → MDR
  • - Enterobacteriaceae (-ve) → MDR - all the sub-types

NOTE:
ESC are Gram-positive
APE are Gram-negative

26
Q

What does pathogenic E.coli cause?

A
  • Most frequent cause of bacteraemia by a gram-ve bacteria.
  • Most frequent cause of community and HAI UTIs.
27
Q

Which antibiotics is E. coli resistant to in many countries?

What is it still sensitive to?

A

Increase in MDR-strains of E. coli.

- 3rdGen cephalosporin resistance (20% in some countries) – most resistance is mediated by the ESBLs.

- Still sensitive to Carbapenems.

28
Q

What are the causes, risk groups, and resistances of Klebsiella pneumoniae?

A

Klebsiella pneumoniae

- Causes – UTIs and respiratory tract infections.

- Risk groups – immunocompromised.

Resistances:

    • 3rdGen cephalosporins, fluoroquinolones and aminoglycosides.
    • CRKP – Carbapenem-Resistant Klebsiella pneumoniae – species of CRE most commonly encountered in the united states.
29
Q

What are the risk groups and resistances of pseudomonas aeruginosa?

A

Risk groups – immunocompromised.

Resistances:

    • High proportions of strains are resistant to several antimicrobials.
    • Carbapenem resistance is above 10% in half EU countries.
30
Q

What is the most important cause of antimicrobial resistant infection in the world?

A

MRSA

  • MRSA expresses an additional penicillin-binding protein (PBP2A) which has a low affinity for methicillin and can therefore function.
  • MRSA strains can therefore still synthesise peptidoglycans.
31
Q

What is the resistance and pathway of VREs?

A

3rd 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.
32
Q

State the target proteins and the method of resistance to the following classes of antibiotics:

a. Cephalosporins
b. Carbapenems
c. Methicillin
d. Vancomycin

A

a. Cephalosporins
Target: Penicillin binding proteins (PBP)
Resistance: Extended-Spectrum Beta-Lactamase (ESBL)

b. Carbapenems
Target: PBP
Resistance: Carbapenemase enzymes

c. Methicillin
Target: PBP
Resistance: alternative target (PBP2A), which has low affinity for methicillin and can function in its presence

d. Vancomycin
Target: peptidoglycan precursor
Resistance: synthesis of a different peptidoglycan precursor

33
Q

What is ESBL encoded on?

What are carbapenemases encoded on?

A

ESBL: Plasmid

Carbapenemases: Transposon