17 - Antimicrobial Peptides (pre-record)

Question 1

What are antimicrobial peptides?

Answer 1

Diverse group, low molecular mass (< 10 kDa), < 50 amino acids, with broad-spectrum antibacterial activity

Question 2

Structure of antimicrobial peptides

Answer 2

Heterogeneous structures, but usually amphipathic and cationic

Question 3

Features of antimicrobial peptides

Answer 3

• Located in phagocytes or epithelial surfaces, one of the earliest developed molecular effectors of innate immunity
• Can also interact with adaptive components, as well as synergizing with other immune molecules
• Chemotactic, can up-regulate cytokines and complement components, assist in wound repair

Question 4

AMPs between 1960 and 1970

Answer 4

1960s: John Spitznagel observed proteins in guinea-pig & rabbit granulocytes that could kill bacteria
1970s: Robert Lehrer isolated 2 antibacterial peptides from rabbits, and other species

Question 5

AMPs in 1981

Answer 5

Hans Boman 1981:
- Observed that insects produced antimicrobial peptides when exposed to bacteria

Question 6

What groups of peptides were isolated by Hans Boman?

Answer 6

• 31–39-amino acid residues long
• Form an amphipathic  helix
• Aggregate on bacterial surface prior to pore formation
• Active against Gram + and Gram – bacteria

Question 7

AMPs in 1986 - Michael Zasloff

Answer 7

Michael Zasloff: 1986 Observed antibacterial resistance in the African frog, Xenopus laevis

Identified 1st amphibian peptide – magainin
- Magainins stored in neuroepithelial cells
- Form bacteria-resistant ‘mesh’
- Amphipathic  helix

Tried to develop therapeutic use for magainins, via Magainin Pharmaceuticals, producing therapeutic cream Locilex™
- FDA refused approval on grounds of insufficient evidence of efficacy
- Zasloff returned to academia

Question 8

What growth of research has there been into AMPs?

Answer 8

• Found in nearly every species studied
• Now > 2,000 known
• Relatively few taxa examined
• No systematic form of nomenclature
• Multiple targets, e.g. anti-viral, anti-fungal, anti-cancer, cytolytic, immuno- modulatory

Question 9

Distribution of AMPs across kingdoms and in animal taxa

Answer 9

KINGDOMS:
- animaliia (73.6%), viridiplantae (16.1%), bacteria (6.4%), fungi (0.6%), other (3.4%)

ANIMAL TAXA:
- amphibia (39%), mammal (27%), insecta (23%), other (11%)

Question 10

What animal taxa has there been receptor AMP interest?

Answer 10

Amphibia – recent interest in AMP activity against fungal pathogens

Question 11

Where are AMPs found in humans?

Answer 11

• blood plasma
• seminal
• amniotic
• urine
• sweat
• airways secretions
• tears
• intestinal mucus
• milk
• cervicovaginal
• saliva

All examples of biofluids

Question 12

Summary of AMPs

Answer 12

Diverse structures, low molecular mass (< 10 kDa), broad-spectrum antibacterial activity

Question 13

Where are AMPs located?

Answer 13

Located in phagocytes or epithelial cells, one of the earliest developed molecular effectors of innate immunity

Question 14

Where were AMPs first noticed?

Answer 14

AMPs first noticed in mammals, but characterized initially in insects and amphibians, found throughout all kingdoms

Question 15

Are there targets of AMPs?

Answer 15

May have multiple targets, e.g. fungi, viruses and be capable of chemotaxis, immune modulation and synergy with other proteins

Question 16

Do AMPs just act on one pathogen?

Answer 16

Several AMPs will act against the same pathogen