Week 4 Flashcards
What does the most popular antibiotic target?
The cell wall
What does B-lactam target?
The cell wall
Do call prokaryotes have an outer membrane
No, just gram negatives
What are the roles of the cell envelope
- controls entry and exit
- protection
What is the cytoplasmic membrane composed of, characterisitic?
Lipid bilayer:
- its lipid composition depends on conditions (ex.temp)
- protein-rich
Semipermeable membrane:
- water and hydrophobic substances diffuse thru
- hydrophilic substances do not
What is the main component of the bacterial cytoplasm?
the bacterial cytoplasm is mainly phospholipids
What type of bond attaches fatty acids to glycerol?
ester bonds
Define: Ampiphatic
Amphipathic: polar and non-polar regions
Name 3 functions of cytoplasmic membrane proteins
Transporters:
- import and export substances
Signal Transduction:
- detect external stimuli
Energy Transduction:
- ETC to generate proton motor force (PMF)
- PMF powers ATP synthesis, transport …
Bacteria are usually in a ______ environment:
a) hypotonic
b) hypertonic
c) isotonic
Bacteria are usually in a hypotonic environment
- they have more solutes in the cell than there are in the environment
What is the major component of the cell wall?
peptidoglycan
What makes gram neg diff from gram positive
gram neg
- thin cell wall
- inner and outer membrane
What are 3 features of PG
1) Strong
- determines cell shape
- protects against osmotic lysis
2) Elastic
- stretches, contracts in response to osmotic pressure
3) Porous, mesh-like
- let in/out nutrients and waste
What is the consequence of the PG being distrupted
if PG is disrupted, the cell becomes more susceptible to osmotic lysis in a hypotonic environment
What happens if bacteria lose PG in an isotonic environment?
They loose shape:
Spheroplast = gram neg
Protoplast = gram pos
Case - Mycoplasmas
Mycoplasmas
- small pleomorphic bacteria
- lack cell wall thus osmotically sensitive so live in others cells, isotonic environment
Why is PG a good antibiotic target?
- on or near surface
- made by most bacteria
- no made by human cells
Name 2 antibiotics that target PG
- B-Lactam
- Vancomycin
Describe the PG structure
- made of sugars and aa
- backbone is a long glycan strand with repeating NAM and NAG disaccharide units
- every NAM bears a peptide chain
- glycan strands are connected to each other thru peptide cross links
What is Lipid II, and what does it contain?
Lipid II: key precursor of PG
- contains monomeric PG subunit (NAM and NAG)
- bound to membrane by UDP
How does lipid II synthesis start?
Lipid II synthesis starts with UDP-NAG, UDP activates NAG
REMINDER: See steps for lipid synthesis on ipad
DO it
What does “alanine racemase” make?
What does D-ala-D-ala ligase make?
What inhibits these?
D-Ala
D-Ala-D-Ala
Cycloserine (antibiotic)
Penicillin Binding Protein (PBP)
- Purpose
- Location
- Needed for:
Domain:
Penicillin Binding Protein (PBP)
Purpose: incorporates Lipid II into PG
Location: periplasm
Needed for:
- cell growth
- cell division
- cell wall recycling
Domain: has a glycosyltransferase domain makes glycan strands, peptide cross links
What does the PBD glycosyltransferase domain do?
the glycosyltransferase domain adds lipid II disaccharide to the glycan backbone of PG
Lysozyme
- function/what does it
- define
- more effective against …
Lysozyme
PG glycan backbone can be degraded by:
- bacterial enzymes for cell wall remodeling
- antimicrobial enzymes
Lysozyme: part of innate immune system
- saliva, tears, milk, mucous
- weaken cells wall
Lysozymes are more effective against gram-positives
- PG is more exposed
- gram neg have outer membrane
Describe the PG peptide chain
-pentapeptide attached to NAM sugar
- amino acid sequence varies
- contains D-aa
- Diamino acid in the 3rd position
Described PG-cross linking in gram negatives
- gram negs form a cross link btwn the 3rd residue (diamino acid) and the 4th residue (carbonyl)
- for a amide bond
- release terminal D-alanine
Described PG-cross linking in gram negatives
- gram positives form peptide chains cross linked thru interpeptide bridge
- bridge is attached to diamino acid
- release terminal D-alanine
Describe the mechanism of Transprptidation
- Cross links are formed by PBP transpeptidase domain
1) PBP forms a complex with peptide
2) diamino acid reacts with complex, forms amid bond
What antibiotic targets the transpeptidase domain?
B-Lactam
B-lactam Antibiotics … What?
B-Lactams: penicillin’s, cephalosporins, carbapenems
- most widely used antibiotic
B-lactam mechanism
- inhibits PBP transpeptidase activity
- B-lactam ring reacts with seine in PBP
- blocks PBP from forming cross links, thus weakens PG leading to cell lysis
- bacteriocidal
