Micro new exam materials

Selective toxicity

ability of drug to kill or inhibit a pathogen while damaging host as little as possible

therapeutic dose

drug level required for treatment of an infection

toxic dose

drug level at which drug becomes too toxic for patient (prodces side effects)

theraputic index

ratio of toxic dose to therapeutic dose

side effects

undesirable effects of a drug on a host cell

narrow spectrum drugs

attack only a few different pathogens

broad-s[ectrum

attacks many different kinds of bacteria

cidal agent

kill the target pathogen

static agent

reversibly inhibits growth of microbes

Mininal inhibitoey concentration

lowest concentration of drug that prevents growth of pathogen (measure how effective antimicribial drugs are)

minimal lethal concentration

-lowest concentration of drug that kills the pathogen (MBC)

-Varries for different bacterial species

-tested by diluting antibiotics

-MLC is higher than MIC

Dilution susceptibility test for MIC

Broth or agar with lowesr concentration showing no growth is MIC

dilution susceptibility test for MLC

if brith used, tubes showing no growth can be subcultured into drug free medium; broth from which microbe cant be recovered is the MLC

disk diffusion test

disks integrated with specific drugs are placed on agar plates inoculated with the test microbe. Drug diffuses into agar, establishing a concentration gradient

zone of inhibition

clear zones (no growth) around disk mean that bacterial growth was inhibited. The wider the zone of inhibition the greater the pathogens susceptibility

Kirby-Bauer assay tests

test strain sensitiveity to multiple antibiotics and the size of the clear zone reflects the relative sensitivity, standardize method for disk diffusion test

The Etest

simular to the disk diffusion but uses a strip rather than a disk, Etest strip contain a gradient of an antibiotic, intersection of elliptical zone of inhibition indicates MIC

Mechanisms of actions of antimicrobials: Cell Wall

Penicillin and vancomyosin

Mechanisims of actions of antimicrobials: cell membrane

Polumyxin and Gramicidin

Mechanisms of action of antimicrobials: DNA synthesis

Sulfa drugs and Quinolones

Mechanisms of actions of antimicrobials: RNA synthesis

Rifamycin B and Antiomycin D

Mechanisms of actions of antimicrobials: Protein synthesis

Aminoglycosides and tetracycline

Peptidoglycan synthesis

1. precursors are made in the cytoplasm (NAG and NAM peptide)

2. they are carried across the cell membrane by a lipid carrier: bactoprenol

3. the precursors are polymerized to the existing cell wall structure by Transglycosylases

4. the peptide side chai9ns are cross-linked by Transpeptidase

The cross bridge formation by tranpeptidase is blocked by ___________ and __________

penicillin and cephalosporins

B-Lactum ring

most crucial feature of molecule of penicillin

it is essential for bioactivity

many penicillin resistant organisms produce B-Lactamase (penicillinase) which hydrolyzes a bond in this ring

Penicillins Mode of action:

1. Blocks the enzyme the catalyzes transpeptidation (formation of cross-links in peptidoglycan)

2. prevents the synthesis of complete cell wall leading to Lysis of cell

   1. acts only on growing bacteria that are synthesizing new peptidoglycan

Beta-lactum antibiotics

Penicillins and cephalosporins

The beta-lactum ring chemically resembles what piece of the peptidoglycan?

D-Ala-D-Ala, this molecular mimicry allows the drug (penicillins and cephalosporins) to bind to penicillin-binding proteins (transpeptidase and transglycosylase)

R groups on penicillin can be modified to generate a specific number of semisynthetic drugs

Natural penicillin

Narrow spectrum penicillin

effectiv eagainst gram + and some Gram - cocci (penicilinase-resistant penicillin)

Penicillinase-resistant penicillin

side chains prevent inactivation by penicillinase enzyme

Broad spectrum penicillin

effective against gram + and Gram - (Beta-lactum ring)

Vancomycin (Cell wall)

• a very large and complex glycopeptide produced by the streptomycete spp.

• binds to D-Ala-DAla terminal and prevents the action of the transglycosylases and transpeptidase

• drug of last resort for penicillin resistant Gram + organisums

  • must be given through IV because of poor absorption

Cephalosporins (cell wall)

Broad spectrum antibiotics that can be used by most Pateints that are allergic to penicillin (structurally simular to penicillin)

Gramicidin (targets cell membrane)

Cycic petide produxed by Bacillus brevis

forms a cation channel, through which ions leak

Polymyxin (colistin) (targets cell membrane)

produxed by Bacillus polymyxa

destorys cell membrane, just like detergent

only used topically

Protein synthesis inhibitors

many antibiotics bind specifically to the bacterial ribosomal proteins or rRNA

Tetracyclines, Macrolides, Chloramphenicol

Aminoglycosides

Bind to the 30S ribosomal subunit, interfere with protein synthesis by directly inhibiting the process and by causing misreading of the messenger RNA

Tetracyclines

Four ring structure

broad spectrum, Bacteriostatic

Target the 30S subunit if the ribosome inhibiting protein synthesis

Macrolides (erythromycin is a specific type)

Broad spectrum, usually bacteriostatic

used when ppl are allergic to penicillin

binds to the 50S ribosomal subunit to inhibit bacterial protein elongation

Lincosamides

produced by streptomyces bacteria

broad spectrum of antibiotic activity against anaerobic microbes; less activity against aerobes

Ex. Clindamycin

Chloramplhenicol

chemically synthesized

binds to the 50s ribosomal subunit to inhibit bacterial protein synthesis

toxic with numerous side effects so only used in life threatening circumstances

Metabolic Antagonists

Acts as Antimetabolites: blocking functions of metablic pathways by completively inhibiting the use of key enzymes

Are structural analogs: molecules that are structurally simular to and compete with, naturally occurring metabolic intermediates to block normal cellular metabolism

Quinolones: Drug that affect dna Synthesis and integrity

Block bacterial DNA gyrase, and so prevent replication

bactericidal

Sulfa Drugs (sulfonamide): Drug that affect dna Synthesis and integrity

-analogs of PABA, a precursor for folic acid

needed for dna synthesis

supplied in diet

Trimethoprim

synthetic antibiotic that also interfers with folic acid production

broad spectrum

can be combined with other drugs to increase efficacy of treatment

Nucleic Acid synthesis Inhibitation

The most commonly used antibacterial drugs that inhibit nucleic acid synthesis function by inhibiting:

• DNA gyrase and topoisomerase (flouroquinolones)

• Rna Polymerase (rifamycins)

Fluoroquinolones

acting by inhibiting bacterial DNA gyrase and Topoisomerase IV

broad spectrum

Intrinsic drug resistance

Occurs due to a property of the microbe itself

Mycoplasma resistance to beta-lactum antibiotics and other cell wall inhibitors simply because these bacteria lack a cell wall

Acquired drug resistance

occurs when there is a change in the genome of a bacterium that converts it from one that is sensitive to an antibiotic to one that is resistant

Why are antibiotics considered secondary metabolites?

because they often have no apparent primary use in the producing organism (not essential for survival but enhance the ability to survive)

Antibiotic resistance genes can be ___________ or they can be part of the ____________

plasmid borne, chromosome

Antibiotic-resistance Mechanisms: 1. modify the target so that it not longer binds to the antibiotic

mutations in the ribosomal proteins confer resistance to Streptomycin

Antibiotic-resistance Mechanisms: destroy the antibiotic before it gets into the cell

• the beta-lactmase enzyme specifically destorys penicillins and cephalosporins

• some organism resist effects through production of Beta-lactamase enzyme

  • other organisms use enzymes that only attack the natural penicillins these enzymes are called penicillinase

Antibiotic-resistance Mechanisms: 3. add modifying groups that inactivate the antibiotic

there are three types of enzymes that modify and inactivate the aminoglycoside antibiotics (Gentamicin)

Antibiotic-resistance Mechanisms: 4. pump antibiotics out of the cell

both specific and nonspecific trandsport proteins

how does drug resistance develope?

vertical evolution and can be through conjugation, transduction, and transformation