Biology 103 - Microbes and You

Lecture 19 Outline

What is penicillin anyway? (antibiotics)


Antibiotic activity shown on agar plate test

1940's Mass penicillin production

Structure of penicillin

Structure of the antiviral agent ribavirin

Structure of tetracycline

antibiotics are organic compounds or peptides that kill or inhibit growth of microorganisms by attacking a specific target
the spectrum of an antibiotic describes its ability to attack certain microbes and not others
for example, some antibiotics are effective against gram (-) bacteria while others are effective against fungi
those antibiotics that are effective against a wide range of organisms are called broad spectrum antibiotics
those antibiotics that are specific for a small range of organisms are called narrow spectrum antibiotics
some antibiotics are bactericidal and kill bacteria
others are bacteriostatic and merely prevent growth of bacteria (thus allowing the immune system to kill off the few bacteria remaining)

Lister first proposed disinfectants for surgery
Ehrlich found the first antibiotics
Fleming discovered penicillin
penicillin is the product of a fungus, Penicillium notatum, a bread mold
its chemical structure includes a beta-lactam ring
natural penicillins, like penicillin G, are narrow spectrum
by making a small change in penicillin, synthetic "cillins", like ampicillin can be made
ampicillin and amoxicillin are synthetic penicillins that now have a broad spectrum of activity
penicillin inhibits the synthesis of bacterial cell walls
many bacteria make cell walls out of peptidoglycan
in peptidoglycan, long-chain polymers of sugars (carbohydrates, polyglycans) are linked together with short pieces of protein (peptides)
penicillin inhibits this cross-linking
cephalosporins are made by a different fungus, but also contain a beta-lactam ring and inhibit peptide cross-linking in peptidoglycan
without a proper cell wall, bacterial cells will lyse and be killed
vancomycin and bacitracin also effect cell wall biosynthesis
these agents block to polymerization of the sugars into carbohydrates
bacteria can become resistant to penicillin by producing an enzyme called penicillinase which breaks the beta-lactam ring

Aminoglycosides are complex organic molecules produced by Streptomyces strains
these include streptomycin and neomycin and are broad spectrum antibiotics against bacteria
streptomycin interferes with bacterial protein synthesis by binding to a specific site on the bacterial ribosome
streptomycin does not effect mammalian ribosomes
selectivity of this type is important for all antibiotics
tetracycline is a very broad spectrum antibiotic made by Streptomyces
tetracycline also inhibits bacterial protein synthesis by binding to a specific site on the bacterial ribosome
it is very mobile and is effective against intracellular parasites
erythromycin is a macrolide, a very complex organic molecule
it is also a bacterial protein synthesis inhibitor

we have looked at two antibiotic modes of action: cell wall biosynthesis inhibitors and protein synthesis inhibitors
there are also antibiotics that target RNA/DNA biosynthesis
sulfonamides the first class of antibiotics found by Ehrlich block folic acid biosynthesis
antifungal compounds generally block a step in the biosynthesis of sterols
sterols are important in maintaining proper plasma membrane functions in fungi
miconazole, often used to treat athlete's foot, is in the azole class of sterol biosynthesis inhibitors
there are few effective antiviral agents (and hence no treatment for the common cold)
amantadine can sometimes be effective although its mode of action is unknown
acyclovir is commonly used for herpes outbreaks
acyclovir acts as nucleic base analog and terminates viral DNA synthesis
AZT is used to fight HIV/AIDS by blocking reverse transcriptase
the antimalarial drug chloroquine is a quinine derivative effective against protozoa

Antibiotic resistance can take three forms:
1. destroy the drug (like penicillinase)
2. prevent the drug from getting the cell or pump it out once it gets in (resistance to tetracycline)
3. alter the target (binding site) of the drug (often through a point mutation in the DNA, changing the gene slightly, and changing the protein it codes for slightly)
resistance factors can arise spontaneously through mutation but more often are passed from one bacteria to another
the resistance factor genes are often found on plasmids
the plasmids can move from one bacteria to another through horizontal gene transfer
this can occur between organisms of the same species or occasionally between unrelated organisms
sometimes, the resistance factor genes are on transposons
transposons are jumping genes
they have special sequences on their ends that allow them to excise themselves (jump out) from the bacterial chromosome or plasmid that they are on
the free transposon can then enter another bacterial cell and insert itself into the chromosome or a plasmid

plasmids with antibiotic resistance genes are often used in genetic engineering
a piece of DNA of interest can be inserted into a plasmid
when the plasmid is put into a bacteria through transformation, the antibiotic resistance gene can be helpful in maintaining the plasmid in the microbe
without a good reason to keep a plasmid, bacteria often reject it or degrade it
if grown on ampicillin, bacteria carrying the ampicillin resistance gene will have a selective advantage over ampicillin-sensitive bacteria
thus the bacterium will have good reason to keep the plasmid we have forced into it
if our gene of interest is also on the plasmid, our gene will be kept as well
then we can study the gene of interest in detail while growing in tame laboratory bacterium like E. coli

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