• Plants and Earth Animals
• Knowledge was transferred via verbal communication and Doctrine of Signatures (supernatural)
• First true antibiotics came from fungi (Penicillium)

• Bacteria and Fungi
• We can extract and modify the drug from bacteria or fungi through selective breeding or modifications. 

A metabolic compound produced by a microorganism with the intent of destroying or inhibiting other microorganisms.

• Natural is taken straight from the microbial producer
• Semisynthetic is modified after being taken from the producer
• synthetic drugs are made in the lab based on original designs from microbial producers 

• Broad spectrum work on a diverse array of microbes
• Narrow spectrum work on a small group of microbes

1. Disrupt cell walls
2. Disrupt cell membranes
3. Disrupt proteins
4. Disrupt nucleic acids
5. Other

To inhibit cell wall synthesis.

It works on young dividing cells, less so with old or dormant cells. 

Inhibit transpeptidase from accomplishing cross-linking. 

They destroy crosslinks. 

Works in the cell wall

B-lactam compounds

Stops NAG and NAM from being formed (inhibit peptidoglycan subunit construction)

Works in the cytoplasm

It inhibits elongation of peptidoglycan. 

Works in the cytoplasm

interfere with protein synthesis or function. The drawback is that although bacterial and human ribosomes are different, uman mitochondria have  a bacterium-like ribosome and can be impacted.

• antibiotics can interfere with the proteins themselves

It interferes with ribosome function specifically the binding to the 30s subunit and it causes mRNA to be misread.

An aminoglycoside

They interfere with other enzymes associated with proteins. 

ex) drug prevents protease from chopping up HIV protein so protein gets packaged but is rendered useless

They get into the pteridine synthetase active site and prevent appropriate substrate (PABA) binding so then no d. acid will be made.

Sulfa stops the pathway.

It blocks entry or release by disrupting H+ dynamics during entry or release. It disrupts pH levels

ex) flu

• Disrupt neuraminidase activity
• Block entry only ex) Fuzeon  prevents entry for HIV 

1. Blocking adsorption
2. Blocking transcription/translation/replication
3. Preventing virion maturation

• produced by leukocytes and fibroblasts
• come in alpha, beta, and gamma
• antiviral and anticancer properties
• Interferon reduces healing time and side effects from certain viral infections
• prevents or reduces symptoms 
• Slows cancer progress
• one of the first defenses your body uses to combat viral infections
• too much interferon can make people psychotic

What are Antibacterial Drugs?

(10 groups)

• B-lactam compounds (interefere with cell wall)
• Penicillin group
• Cephalosporin
• Aminoglycosides
• Gentamicin
• Streptomycin
• Tetracyclines (interfere with ribosome functions)
• Chloramphenicol
• Vancomycin (clyndamicin, erthroymycin, rifamycin) 
• Polymyxin and Bacitracin
• Sulfonamides (Sulfa Drugs)
• Sulfones
• Trimethoprim
• Oxazolidones

• Macrolide polyenes
• Amphotericin B
• Nystatin 
• Griseofulvin
• Azoles
• Flucytosine (cytosine analogue) 
• halts fungal replication

• Chloroquine and primaquine  are used or Malaria.
• Quinacrine, sulfonamides, tetracylcines
• Metronidazole for amoebas

Eukaryotes:

• Mebendazole
• T(h)iabendazole
• Piperazine and pyrantel - paralyze muscles
• Niclosamide
• Ivermectin

• Intrinsic
• Microbes that produce antimicrobials must be resistant to their own products
• not a major concern 
• Acquired
• Mutations, recombination, a major concern

• Jumping genes, may hop from chromosome to plasmid, vice versa, or within a type.
• Some jumps are good and others are bad.
• They can replicate before a jump. 
• Two transposons next to each other can jump jointly.

• hospitals are a reservoir for drug resistant genes and natural selection
• Drugs in livestock feeds
• lack of drug regulation
• broad-spectrum drugs used more often

1. Inactivate the drug
2. Decrease drug permeability
3. Increase drug elimination
4. Change drug target
5. Change metabolic pattern

• Allow the drug in but then have an enzyme act on it and render it dysfunctional.
• examples: B-lactamases
• Cephalosporinase and Penicillinase
• May be inherent or acquired

By not letting the drug in: changing the transport mechanism ( change the external receptor)

• Bacteria change porins and other gate keepers so that the drug cannot enter. 
• ex) blocking penicillin entry

They can allow the antiviotic in but spit it back out through an efflux pump. 

• A single pump often works against multiple drugs
• ex) tetracycline resistance

• Change ribosome structure so that aminoglycosides don't work.
• Change structure of protein (ex. change cell wall proteins so that vancomycin doesnt work)
• Change composition of target (ex) reduce expression of ergosterol so amphotericin B doesnt work)

• Choose a different metabolic option (ex. use an alternative pathway to make folic acid) 
• Stop a metabolic activity and either switch to a new one or wait til a drug is gone and then pick the activity up again

1. Targeting siderophores
2. Targeting riboswitches
3. Pre-and pro-biotics
4. Lantibiotics

• Drugs that target siderophores interfere with microbial iron acquisition activities
• ex) S. aureus and its habit of punching holes in red blood cells to steal iron from heme

They stimulate growth of mutualistic bacteria in the gut. The beneficial bacteria can outcompete potentially infectious bacteria.

It is an encouragement strategy. 

Live cultures of mictobes fed deliberatley to a person to help re-establish normal intestinal or cutaneous flora. 

ex) AquaFlora for beneficial Candida albicans (yeast state vs. mycelium state)

mycelium state is harmful, but yeast state is hardier than mycelium state and will outcompete with it. 

• Inhibit polymerases/interfere with associated enzymes
• disrupt nucleic acids