Major gram neg bacterial pathogens

Question 1

Name the gram negative surface antigens

Answer 1

H-antigen = flagellum
K-antigen = capsule
Peptidoglycan
O-antigen = outer membrane lipopolysaccharide (LPS)

Question 2

Both gram neg and gram pos bac have a capsule - what is it’s purpose?

Answer 2

Protection and help it stick down to surface

Question 3

What does PS o-antigen do?

Answer 3

Deters complement c567 - Membrane attack precursors (MAC)

Question 4

Structure of gram neg bac?

Answer 4

2 membranes
OM connected to LPS layer
Thin PG layer
Does NOT retain gram stain = pink
Outer layers and released are LPS major antigens
LPS and capsule help immune evasion

Question 5

Give examples of medically important gram neg bac

Answer 5

Neisseria - meningitis and gonorrhoea
Haemophilus influenza - meningitis, pneumonia
Pseudomonas aeruginosa - burn infecs and lung infecs of CF pts
Yersinia pestis - plague
Bordetella - whooping cough
Legionella - legionnaires disease
Treponema pallidum - syphilis

GI:
Salmonella spp - gastroenteritis
Shigella spp - gastroenterits
Virbio cholera - cholera
Helicobacter pylori - stomach ulcers
Campylobacter jejuni - food poisoning

Question 6

What is neisseria spp?

Answer 6

Gram neg diplococci

Question 7

Name the pathogens of neisseria spp and what do they do?

Answer 7

N-meningitidis;

• Meningitis/meningococcal septicaemia
• Infec of CSF and meninges
• Commensal carriage in pharynx/nasopharynx
• Capsular, serotyping based on polysaccharides

N/gonorrhoeae;

• Gonorrhoea
• STI, genital and oral infec
• Neonatal transfer - eye infecs
• Lipopolysaccharide capsule often sialylated

Both fastidious - Growth (Heated blood [chocolate}) + CO2

Question 8

What is meningitis?

Answer 8

Inflam of the meninges
Bac replicates in cerebrospinal fluid, produce lots of protein = meninges inflamed = pressure on brain = aching
Also gives rash, leg pain, cold hands and feet, vomiting, confusion

Question 9

What is N.meningitidis carriage rate? When may the carriage rate increase?

Answer 9

10-25% nasopharynx commensal carriage rate

During disease = carriage rate may rise to 90%

Question 10

What do N.meningitidis’ serogrpoups depend on? Name the 5 serogroups

Answer 10

Dependent on polysaccharide capsular antigen
A, B, C, Y, W135 - account for almost all cases worldwide
UK - 90% serogroup B
A, C and W135 comprise others

Question 11

N.meningitidis pathogenesis - how does it spread?

Answer 11

Directly to subarachnoid space or through nasopharyngeal mucosa to enter the bloodstream
Mucosal spread - kissing

Protease IgA for serum resistance
In most 1st infecs = Ab production without dev of disease
Bactericidal antibody against capsule is most important protective factor

Question 12

N.meningitidis epidemiology?

Answer 12

Outbreak in winter
2000 cases and 80 deaths in UK per yr
2/3 of cases occur in 1st 5yrs of life
Peak prevalence = 1st yr of life, 2nd peak = 16-23
Frequent in young adult pop - uni, military

Question 13

Where is the highest occurrence of meningitis?

Answer 13

In a region of sub-saharan Africa - meningitis belt

Infec of up to 10% of pop - mainly serogroup A

Question 14

How to diagnose meningitis?

Answer 14

CSF - many PMNLs, presence of bac - diplococci
Blood culture;
- Sub-culture on chocolate agar
- Sugar fermentation tests - maltose and glucose positive (red to yellow)
- Oxidase positive (purple)

Question 15

How to treat meningitis?

Answer 15

Penicillin, cefotaxime

• followed by eradicative treatment (rifampicin or ciproflaxacin often with corticosteroids
• Vaccines available for group A, C, Y and W135
• 4CMenB vaccine in 2015 for infants and at-risk groups
• Expensive

Question 16

What does haemophilus influenzae (gram neg cocco-bacillus) cause? Complications? Survival percentage?

Answer 16

Non-invasive disease: otitis media, sinusitis (2-4yrs old)

Cause septicaemia, pneumonia and meningitis

• Meningitis and pneumonia (4 months to 2 yrs old)
• Invasion - penetration of submucosa of nasopharynx
• Complications; epiglottitis, bacteraemia, cellulitis
• 15-35% survivors with disability

Question 17

H.influenzae pathogenesis?

Answer 17

6 capsular types (a-f`)
Some strains non-capsulate (commensals)
- capsular major virulence factor avoidance of c3b binding
- 99% invasive disease caused by type b capsular type

Commensal carriage of type b 5-10% nasopharynx, non-capsular 25-80%

Question 18

H.influenzae epidemiology?

Answer 18

Serious systemic disease in children
300,000 deaths per yr in 2008 - mainly in dev countries
Outbreaks in nursery

Question 19

H.influenzae vaccine?

Answer 19

Hib vaccine given at 2, 3, 4 months
Cost of vaccine has been reduced
Increasing antibiotic resistance = vaccine needed more

Question 20

How to diagnose presence of H.influenzae?

Answer 20

Sputum, throat swabs, blood culture

Chocolate gar 5-10% CO2

Question 21

What does haemophil need for growth?

Answer 21

Factor X (haemin) or V (NAD or NADH)
H.influenzae = needs both X and V
H.ducreyi needs X

Question 22

How to diagnose meningitis - H influenzae?

Answer 22

Antigen detection/PCR

Question 23

How to treat H.influenzae?

Answer 23

Cefotaxime
Non-invasive disease - amoxycillin
Chemoprophylaxis for contacts - rifampicin

Question 24

What causes the plague?

How is it spread?

Answer 24

Yersina pestis

Infected flea bites human

Question 25

Yersinia pestis virulence factors?

Answer 25

Gram neg so LPS
Contains 3 large virulence plasmids
Encode type III secretion needle for injection of toxins into host cell: suppress immune response, promote bacterial invasion and survival inside host cells
pCPI - plasminogen activator: helps dissemination (spread) in host - degrades complement components C3b and C5a
pMTI - antiphagocytic capsule and TTSS host evasion

Question 26

Mortality rates of the plague?

Answer 26

100% for pneumonic plague, 50% for bubonic plague

Killed 25% of european population, 30% in England

Question 27

How was spread of the plague controlled?

Answer 27

Quarantine - on who entered, food dropped at perimeter

Question 28

How is the plague treated today?

Answer 28

Streptomycin or tetracycline
Formalin-killed vaccine
Some outbreaks in 3rd world

Question 29

Give an example of an opportunistic pathogen

Answer 29

Pseudomonas aeruginosa

Question 30

Pseudomonas aeruginosa features?

Answer 30

Common environmental isolate and human commensal
Gram neg, motile rod motile, aerobic
Often multiply antibiotic resistant
Major causes of infec after burns
Many extracellular proteases breakdown tissues
Well adapted to warm moisture in a burn wound
Can lead to septicaemia - Ecythma gangrenosum lesions
Major killer of cystic fibrosis pts - who become chromosomally infected

Question 31

What is ESKAPE?

Answer 31

Group of most antibiotic resistant pathogens with highest risk in clinical and hospital situations
4/6 = gram neg = biggest worry as increasingly resistant to last drugs of resort - Carbepenam resitant strains = most scary

Enterococcus faecum (gram pos)
Staphylococcus aureus (MRSA) (Gram pos)
Klebsiella pneumoniae (gra neg)
Acinetobacter (gram neg)
Pseudomonas (gram neg)
Enterobacter (gram neg)