Chapter 10 Controlling microbial growth in the body Flashcards
Chemicals that affect physiology in any manner is called drugs, give some examples
Caffeine, alcohol, and tobacco
Drugs that act against diseases are called? (Any chemical to treat or apply to any treatment to treat any human condition)
Chemotherapeutic agents, examples are insulin, anticancer drugs, and drugs for treating infections called antimicrobial agents (antimicrobials)
What did Paul Ehrlich (1854-1915) do?
- A visionary germen scientist
- Proposed chemotherapy to describe use of chemicals that selectively kill pathogens while having little or no effect on patient
- He wrote of “magic bullets” that would bind to receptors on germs to bring about their death while ignoring host cells, which lacked the receptor moleucles
- His search resulted in the discovery of one arsenic compound that killed trypanosome parasites & another that worked against the bacterial agent of syphilis.
What did Alexander Fleming do?
- British bacteriologist, he reported that antibacterial action of penicillin released from Penicillium mold, which creates a zone where bacteria can’t grow
Back in the day Ehrlich’s arsenic compounds were toxic to humans, and penicillin was not available in large quantities to be useful until the late 1940s so what was used instead?
Sulfanilamide, discovered in 1932 by the German chemist Gerhard Domagk was the first practical antimicrobial agent efficacious in treating a wide array of bacterial infections
What did Selman Waksman discover?
Other microorganisms that are sources of useful antimicrobials, most notably species of soil-dwelling bacteria in the genus Streptomyces. Waksman coined to term antibiotics to describe antimicrobial agents that are produced naturally by an organism
Drugs that are effective against antiviral agents are likely?
Toxic to the host as well because viruses utilize their host cell’s enzymes & ribosomes to metabolize & replicate
Because there are many differences between the structure & metabolism of pathogenic bacteria & their eukaryotic hosts, antibacterial drugs make greatest number & diversity of antimicrobial agents. Why are there few anti fungal?
Fewer anti fungal & antiprotozoan drugs are available, why is this? Because fungi, protozoa, & helminths-like their animal & human hosts- are eukaryotic & thus share common features.
Antimicrobial drugs can be categorized into several general groups according to their mechanism of action
1) Drugs that inhibit cell wall synthesis
2) Drugs that inhibit protein synthesis (translation)
3) Drugs that disrupt unique components of cytoplasmic membrane
4) Drugs that inhibit general metabolic pathways not used by humans
5) Drugs that inhibit nucleic acid synthesis
6) Drugs that block a pathogens recognition of or attachment to its host
Drugs that inhibit cell wall synthesis. These drugs are?
Selectively toxic to certain fungal or bacterial cells, which have cell walls, but not to animals, which lack cell walls
Drugs that inhibit protein synthesis (translation) by?
Targeting the differences between prokaryotic & eukaryotic ribosomes
Describe how drugs can inhibit the synthesis of bacterial walls
- They prevent cross linkage of NAM subunits which connects to the nag subunits which form the peptidoglycan.
- Beta-lactams- most prominent drug, several types, penicillins & cephalosporins
What does the Beta-lactam drug do?
Inhibits synthesis of peptidoglycan bacterial walls by irreversibly binding to the enzymes that cross-link NAM subunits.
* Their functional portions are the beta-lactam rings
What are the semisynthetic derivatives of beta-lactams?
It is where chemists have made alterations to natural beta-lactams, such as penicillin G, to create semisynthetic derivatives. In turn they are:
1) More stable in the acidic environment of the stomach
2) More readily absorbed in the intestinal tract
3) Less susceptible to deactivation by bacterial enzymes
4) More active against more types of bacteria
The simplest beta-lactams are?
Monobactams, which are seldom used because they are effective only against aerobic Gram-negative bacteria
What do the antimicrobials vancomycin and cycloserine do?
They disrupt cell wall formation by directly interfering with particular alanine-alanine bridges that link the NAM subunits in many Gram-positive bacteria. The bacteria that lack these bridges are resistant.
What does bacitracin do?
It blocks the transport of NAG and NAM from the cytoplasm out to the wall. Like beta-lactams, vancomycin, cycloserine, and bacitracin result in cell lysis due to the effects of osmotic pressure
Why are dormant cells unaffected with drugs that inhibit synthesis of bacterial walls?
Because those drugs prevent bacteria from increasing the amount of cell wall material but have no effect on existing peptidoglycan, they are effective only on bacterial cells that are growing or reproducing
What does isoniazid (IHN) and ethambutol do?
They disrupt the formation of my colic acid in Mycobacterium species. These drugs must be administered for months or years to be effective because Mycobacteria typically reproduce only every 12-24 hours
Why is the inhibition of protein synthesis significant?
Because cells use proteins for structure & regulation, as enzymes in metabolism, & as channels & pumps to move materials across cell membranes. Thus a consistent supply of proteins is vital for the active life of a cell. All cells use ribosomes to translate proteins using info from mRNA templates
Prokaryotic ribosomes differ from eukaryotic ribosomes in structure & size and many antimicrobial agents take advantage of the differences between the ribosomes to?
Selectively target bacterial protein translation without affecting eukaryotes.
However, because some of the drugs affect eukaryotic mitochondria which contain 70s ribosomes like prokaryotes, these drugs can be harmful to animals & humans, especially the active cells of the liver & bone marrow.
Both the 30s and 50s subunits of prokaryotic ribosomes play a role in?
Why is this important?
The initiation of protein synthesis, in codon recognition, & in the docking of tRNA-amino acid complexes, & that the 50s subunit contains enzymatic portion that forms peptide bonds.
This is important because in order the understand the actions of antimicrobials that inhibit protein synthesis we need an understanding of the process of translation, because various parts of ribosomes are targets of drugs
The antimicrobials that target the 30s ribosomal subunits are?
Aminoglycosides and tetracyclines
Aminoglycosides such as streptomycin and gentamicin do what?
Change the shape of the 30s subunit making it impossible for the ribosome to read the codons of mRNA correctly
Some amino glycosides and tetracyclines block what?
The tRNA docking site (A site), which then prevents the incorporation of additional amino acids into a growing polypeptide
Some antibacterial drugs, such as the short polypeptide gramicidin, disrupt the cytoplasmic membrane of a targeted cell often by?
Forming a channel through the membrane, damaging its integrity. This is also the mechanism of action of a group of anti fungal drugs called polyenes
What do the polygenes nystatin and amphotericin B (major drug) do?
They are fungicidal because they attach to ergosterol, a lipid constituent of fungal membranes, in this process disrupting the membrane & causing lysis of the cell. The membranes of humans are somewhat susceptible to amphotericin B because they contain cholesterol, which is similar to ergosterol, though cholesterol does not bind amphotericin B as well as ergosterol
Causes change in 30s ribosome shape, so mRNA is misread
Some aminoglycosides, for example streptomycin
Block docking site of tRNA
Tetracycline and some aminoglycosides
Blocks peptide bond formation
Chloramphenicol
Bind to 50s subunit, blocking proper mRNA movement through ribosome, & synthesis stops
Lincosamides or macrolides
Azoles, such as fluconazole, and allylamines, such as terbinafine, are two other classes of anti fungal drugs that disrupt cytoplasmic membranes. They act by?
Inhibiting the synthesis of ergosterol, without this the cell’s membrane does not remain intact & the fungal cell dies. These drugs are generally harmless to humans, because human cells don’t have ergosterol
