Pharmacology 2060A/B Lecture Notes - Lecture 16: Topoisomerase, Hives, Dna Replication

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Antibiotics
Bacteria
Bacteria are single celled organisms that can be shaped as rods, spheres, or spirals
Bacteria occupy almost every habitat on Earth, including humans!
Most bacteria are rendered harmless by our immune system and some even play beneficial roles
However, some bacteria are pathogenic and cause diseases such as cholera, syphilis and tuberculosis
Before the discovery of antibiotics, bacterial infection was a major cause of morbidity and death
Bacterial Pathogenicity
Bacteria have a number of virulence factors that they use to cause infection:
oFimbriae and pilli
oFlagella
oSecretion of toxins and enzymes
oInvasion
Fimbriae and Pilli
Fimbriae and pilli are hair like structures that project from the surface of bacterial cells
They allow bacteria to attach to certain sites in our body so they are not washed away
For example, the bacteria E. coli are known to cause bladder infections
E. coli produce fimbriae that attach to the urogenital tract
Flagella
Bacteria typically live in aqueous environments and need to move to sites where they can survive
The flagellum that bacteria possess allows them to “swim” through the watery environment of our body to
the site where they may survive
Toxins and Enzymes
Some bacteria secrete toxins and/or enzymes
Secreted toxins can have a wide array of effects including nausea, vomiting, diarrhea, cramps, pain, fever,
or even paralysis
In some cases, bacterial toxins produced outside of our body can mediate toxic reactions if they gain entry
to our body. A good example is what occurs in some cases of poisoning
In addition to toxins, bacteria also release enzymes. Some of these enzymes can degrade tissue or
breakdown antibodies, our defense against infection
Invasion
Some bacteria can actually invade (enter) our cells
For example, the bacteria that cause Salmonella invade cells of the intestine and cause severe diarrhea
Bacteria that cause tuberculosis usually enter our body in the lungs and can “hide” inside cells making it
impossible for our immune system to act on them
Gram Staining of Bacteria
Gram staining is a technique that is used to classify bacteria as either gram positive or gram negative
Why is this classification important? The gram stain tells us about the cell wall structure of bacteria, in
particular the amount of peptidoglycan. This can be important in the determination of which antibiotic we
use
Gram positive cells have a thick peptidoglycan wall that stains purple during gram staining
Gram negative cells have a thin peptidoglycan layer and stain pink during gram staining
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Gram Positive vs. Gram Negative Bacteria
Notice the thin peptidoglycan layer (cell wall) in the gram negative bacteria compared to the thick peptidoglycan
layer in the gram positive bacteria. Also notice how the gram negative bacteria has an outer membrane, whereas that
gram positive bacteria doesn’t
Gram Positive Gram Negative
Thick peptidoglycan layer (cell wall) Thin peptidoglycan layer (cell wall)
Techoic acids- provide ridigity to the cell wall. The major
surface antigen in gram positive bacteria
Do not have techoic acids
Do not have LPSs Lipopolysaccharides (LPSs)- are a structural component of the outer
membrane and the major surface antigen in gram negative bacteria
Do not have an outer membrane Outer membrane- protects gram negative bacteria from bile salts and
detergents
Do not have porins (a few exceptions) Porins- on the outer membrane. Allow certain sugars, ions and amino acids
to enter the bacteria
Signs of Infection
The typical signs of infections include fever, overall malaise, local redness, and swelling
Other signs of infection include increased respiratory rate and tachycardia
In some cases patients may not have a fever despite having an infection. For example, newborn babies may
have an immature hypothalamus or the elderly may have decreased hypothalamic function. The
hypothalamus is important in regulating body temperature
There may be other signs of infection depending on the location of the infection. For example, patients with
a urinary tract infection feel the frequent need to urinate
Selective Toxicity
The treatment of a bacterial infection is critically dependent on the ability to produce selective toxicity
Selective toxicity means the therapy is able to destroy the bacteria without harming the host (i.e. human
cells)
Selective toxicity is produced by targeting differences between the cellular chemistry of bacteria and
humans
Antibiotic therapy produces selective toxicity by:
oDisrupting the bacterial cell wall (human cells do not have a cell wall)
oTargeting enzymes that are unique to bacteria
oDisrupting bacterial protein synthesis (bacterial and human ribosomes are different)
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Selection of the Proper Antibiotic
Several questions must be considered when selecting an antibiotic including:
1. Has the infectious bacteria been identified?
2. Bacterial sensitivity to the antibiotic?
3. Can the antibiotic access the site of infection?
4. Is the patient able to battle the infection?
Identification of the Bacteria
Ideally, bacteria are identified prior to selection of the treatment
The gram stain is a rapid test that provides information on the structural features of the bacteria
In general, culturing the bacteria to properly identify it will provide the best basis for selection of the
therapy
In some cases, cultures are not possible or reliable for identifying the bacteria. For example, cultures are
rarely taken from children who have an ear infection because they are difficult to obtain. In addition,
samples from patients with lower respiratory infections may contain several species of bacteria
Bacterial Sensitivity to the Antibiotic
Antibiotics can be bacteriostatic or bactericidal
Bacteriostatic
oStops the growth and replication of bacteria and in doing so, stops the spread of infection
oThe body’s immune system can then attack and remove the bacteria
Bactericidal
oDrugs kill the bacteria
Microbiologists can culture bacteria and determine the minimum inhibitory concentration (MIC) and the
minimum bactericidal concentration (MBC) of antibiotic drugs
Antibiotic Concentration
Penetration to the Site
Some infections are difficult for antibiotics to penetrate. These infections require careful selection of antibiotics that
are able to penetrate to the site of action
Meningitis
Urinary Tract Infections
Osteomyelitis
Abscesses
Otitis Media
Meningitis
Is an infection of the meninges, which are the membranes that cover the brain and spinal cord
Bacterial meningitis is rare but is much more serious than viral meningitis (life threatening)
Many antibiotics are unable to penetrate the meninges
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