Bacterial capsules

Question 1

Def. capsule, slime

Answer 1

polysaccharide layer that lies outside the cell envelope, attached to outer surface

slime: polysaccharides around bacterium, not attached

Question 2

Relevance of capsule

Answer 2

non-encapsulated strains: strongly decreased pathogenicity

Question 3

Examples for encapsulated bacteria

Answer 3

Gram-pos: Bacillus, anthracis, Strpetococcus pneumoniae

Gram-neg: Klebsiella penumoniae, Hemophillus influenzae, Neisseria meningitidies

Question 4

Bacillus anthracis - disease?

Answer 4

Anthrax (cutaneous A. or inhalation A.)

Question 5

Virulence of B. anthracis

Answer 5

Poly-D-glutamate capsule mediates invasive stage, depends on pX=2 plasmid.
Anthrax toxin mediates toxic stage, depends on pX01 plasmid, 2 subunits.
Vaccnie available.

Question 6

Streptococcus pneumoniae - disease

Answer 6

Non- encapsulated: normal inhabitant of human upper resp. tract
Encapsulated: community aquired pneumonia, sinusitis, meningitis etc
Leading cause of invasive bact. disease in children/elderly!

Question 7

S. pneumoniae - capsule

Answer 7

Functions as adhesion, important for formation of biofilms.

Inhibits recognition of C3b (complement) > phagocytosis resistance. Antigenetic variation.

Question 8

Important: antigenic variation of S. pneumoniae

Answer 8

up 90 known serologically different capsular types > immunologically each serotype is distinct pathogen > same pathogen can cause diseases many times in same organism

(serotype switching by replacing cps locus)

Question 9

Important: Polysaccharide (PS) antigen immune response

Answer 9

Are T-cell-independent: activation of (almost) only B cells, no intrinsic B cell stimulating activity, predominant ab isotypes: IgM (IgG2).

(IgM/G2 no/weak binding to Fc receptors of granulocytes)
(but: IgM-C1q interaction > complement)

Question 10

Protein vs PS antigens

Answer 10

Protein: T-cell-dependent ag presentation > cytokine release > prolif, IgG class switching, memory B cells

PS ag: T-cell-independent ag presentation (signal 1: PS cross-links Abs, signal 2: IL2/3 binding) > prolif, IgM (IgG2) release > no Ig class switch, no memory B/T cells

Question 11

S. pneumoniae -vaccines

Answer 11

1. Polysaccharide-vaccine (problematic)
2. Conjugate vaccines (conjugation of PS to carrier protein > T-cell-dependent ag)
3. Alternative strategies (protein antigens, polysaccharide peptide mimics, DNA vaccines)

Question 12

Klebsiella pneumoniae - disease

Answer 12

Nosocomial pneumonia (Aritifical respiration: proton pump inhibitors > less gastric acids>bactaria enter)

prominent polysaccharide capsule (K ag)

often antibiotic-resistant

Question 13

Hemophilus influenzae

Answer 13

Requires X (hemin) and V (NAD) for growth.

Capsule is major VF (of six types, b is human-pathogenic > PRP-capsule)

Conjugate vaccines with different carrier proteins available.

Question 14

Neisseria meningitidis - disease

Answer 14

Non-capsulated: in upper respiratory tract of many people

Capsulated: invasive disease, meningitidis

Question 15

N. meningitidis VF

Answer 15

LPS, fimbriae, capsule

Capsule: diff types, cause of disease: A/B/C/W-135/Y

Question 16

Important: mechanisms of N.meningitidis to change its surface in face of selective pressure

Answer 16

1. variable gene expression by strand mispairing of varibale number tandem repeat regions during DNA replication
   (nadA: Neisseria adhesion, porA porin, siaD:polysialyltransferase > capsule biosynthesis)
2. horizontal gene transfer during cocolonization of human nasopharynx with at least two strains > capsular switching

Question 17

Important: serotypes of Neisseria meningitidis

Answer 17

Europe: 70-75% serogroup B, 20-25% serogroup C

Sub-Saharan Africa. A

A: N-acetyl-D-mannosmain-1-phosphate
B/C/w-135/Y: sialic acid

Question 18

Meningococcal vaccines

Answer 18

A) Polysaccharide vaccines
B) Conjugate vaccines

Serogroup B vaccines: difficult - structural homology to human N-CMA, 3 diff surface proteins that are not PS are used now

Question 19

PS vs conjugate vaccin

Answer 19

PS: T-cell-independent immune response
conjugate: T-cell-dependent