Antimicrobials I

Front 1

How do antimicrobials kill/inhibit microbes without killing/inhibiting the patient?

Back 1

Exploit subtle biochemical differences between humans and microbes

Front 2

What is a bactericidal agent?

Back 2

An agent that kills bacteria.

Front 3

What is a bacteriostatic agent?

Back 3

An agent that inhibits bacterial growth but does not kill.

Front 4

What is the difference between intrinsic resistance and extrinsic resistance?

Back 4

Some species are always resistant to some antibiotics while others can become resistant by mutation or by receiving a resistance gene from another species.

Front 5

_____ ______ _____ is the lowest concentration of antimicrobial agent that will inhibit bacterial growth in vitro. (Used in the lab)

Back 5

Minimal inhibitory concentration
(MIC)

Front 6

What is the ratio physicians should use when treating an infection?

Back 6

Physicians should aim for a ration of 4 times the MIC at the site of infection.

If 4 times the MIC does not work then the bacteria is said to be resistant to that antibiotic.

Front 7

What are the three general mechanisms of resistance?

Back 7

1. Altered uptake
2. Inactivation
3. Altered target (increase amount of enzyme or mutate the enzyme)

Front 8

How do cell wall biosynthesis inhibitors work?

Back 8

All of these agents prevent formation of peptidoglycan.

Front 9

True or False.

Gram positive and gram negative bacteria are susceptible to inhibitors of cell peptidoglycan biosynthesis.

Back 9

TRUE

*However, in gram negative bacteria the inhibitor must be able to cross the outer membrane through porins to reach the peptidoglycan layer!

Front 10

Where is peptidoglycan precursor made?

Back 10

The peptidoglycan precursor is a disaccharide that is made inside the cell.

Front 11

Where are the chains of peptidoglycan assembled?

Back 11

They are assembled outside the cell in chains of 10-65 disaccharide units

Front 12

What happens to make these chains more rigid?

Back 12

Peptidoglycan chains are cross-linked to provide rigidity.

Front 13

Where does cross-linking occur?

Back 13

Cross linking is from the terminal D-Ala D-Ala of one peptide side chain to the NH2 group of another side chain.

Front 14

What is the common feature for all of the beta-Lactam antibiotics?

Back 14

All contain a four-membered lactam ring

Front 15

How do the major classes of beta-lactams differ?

Back 15

Major classes of beta-lactams differ by their 2nd ring and an R group

Front 16

What is the mechanism of action for beta-lactams?

Back 16

beta-Lactam antibiotics act by inhibiting a set of enzymes called transpeptidases and carboxypeptidases that catalyze cell wall cross linking.

Front 17

What do beta-lactams structurally resemble?

Back 17

beta-lactams structurally resemble the D-Ala D-Ala part of peptidoglycan molecules and bind the active site of transpeptidases and carboxypeptidases

Front 18

What is another name for transpeptidases and carboxypeptidases?

Back 18

Because these enzymes bind penicillin they are called "penicillin binding proteins" (PBPs)

Front 19

Bacteria contain multiple PBPs that are involved in ______ and _______ of the peptidoglycan layer of the cell wall.

Back 19

PBPs are involved in generation and maintenance of the cell wall

Front 20

True or False.

Bacteria contain multiple PBPs which have different roles in cell metabolism and also have different affinities for different beta-lactams.

Back 20

True.

Front 21

beta-lactams become covalently bound to the PBP so the enzyme is inactivated and blocks _______.

Back 21

cell wall biosynthesis

Front 22

beta-lactams are generally bactericidal/bacteriostatic?

Back 22

Bactericidal

Front 23

Why are beta-lactams only bacteriostatic in certain notable bacteria?

Back 23

Some bacteria, such as enterococci and some strains of staph and strep, do not produce active autolytic enzymes so they are said to have "tolerance".

Front 24

What happens after cell wall biosynthesis is blocked by beta-lactams?

Back 24

Block in cell wall synthesis leads to cell lysis by bacterial autolysins.
Autolysins normally allow for insertion of new peptidoglycan material and septum formation but can also degrade peptidoglycan in absence of synthesis.

Front 25

What is the most common mechanism for inactivation of beta-lactams?

Back 25

Inactivation via a beta-Lactamase

*beta-lactamases are found in gram positive and negative bacteria

Front 26

Gram negative bacteria have a large number of unique beta-lactamases.
_________ is a beta-lactamase found encoded on the chromosome of virtually all gram negative bacteria.

Back 26

Cephalosporinases

(most active against cephalosporin)

Front 27

What can be added to an beta-lactam to counteract inactivation by beta-lactamases?

Back 27

beta-lactamase inhibitors are added to antibiotics such as augmentin

Front 28

How are PBP genes altered to resist antibiotic action?

Back 28

Mutation
Recombination (transformable S. pneumoniae)
Acquisition of a new PBP (MRSA)

Front 29

What are some examples of glycopeptide antimicrobials?

Back 29

Vancomycin
Teicoplanin

Front 30

What is the mechanism of action for glycopeptide antimicrobials?

Back 30

Also inhibit cross-linking but instead of binding the active site of PBPs will bind the substrate, D-Ala D-Ala to prevent access to the cell wall enzymes

Front 31

_______ bacteria are intrinsically resistant to vancomycin.

Back 31

Gram negative

*Vancomycin cannot get through the outer membrane.

Front 32

How are vancomycin-enterococci resistant?

Back 32

The peptidoglycan cross-linking peptide terminates as D-Ala D-lactate instead of D-Ala D-Ala which is not recognizable by the drug.

Front 33

How did MRSA become vancomycin resistant?

Back 33

MRSA aquired a plasmid borne transposon containing the resistance gene from Enterococcus faecalis. This eliminated an important treatment option for MRSA.

Front 34

What is cycloserine a structural analog of?

Back 34

Structural analog of D-Ala

Front 35

What is the mechanism of action for cycloserine?

Back 35

Block the alanine racemase and D-Ala ligase to inhibit cell wall biosynthesis.

Front 36

What does alanine racemase catalyze?

Back 36

Converts L-Ala to D-Ala

Front 37

What does D-Ala ligase catalyze?

Back 37

Catalyzes synthesis of the D-Ala D-Ala peptide used for cross linking.

Front 38

Why must cycloserine penetrate the cytoplasmic membrane?

Back 38

D-Ala ligase resides in the cytoplasm

Front 39

What is the mode of action for bacitracin?

Back 39

Prevents recycling of the undecaprenol carrier that transports the peptidoglycan precursor from the cytoplasmic side to the outside of the membrane.