Chapter 27 Antimicrobial Drugs and Drug Resistance

Cephalosporins

targets cell wall synthesis by preventing cross-linking of peptidoglycan on a broader spectrum.

Penicillins belong to the ____ group of antibiotics.

Beta-lactam

How does isoniazid inhibit bacterial growth? What bacterial types does it affect? Based on this would you say it has a narrow spectrum or a broad spectrum of activity?

Isoniazid inhibits bacterial growth by interfering with the syntheses of mycolic acid (a mycobacterial cell wall component). Isoniazid controls and treats tuberculosis. It is a narrow-spectrum antibiotic.

Antiviral Drugs

Reverse Transcriptase Protease Inhibitors Fusion inhibitors interferons neuraminidase inhibitors

Is there a correlation between antibiotic use and number of resistant strains of microorganism? Explain the pattern seen

Yes. The more often antibiotics are used, the more resistant the bacteria becomes.

"Antibiotic drug resistance"

acquired ability of a microorganism to resist the effects of an antimicrobial agent to which it is normally susceptible.

We refer to naturally occurring antimicrobial drugs as

antibiotics

Prokaryotic (bacterial) ribosomes

are 70S particle units with 30S and 50S subunits. Ribosomes are free-floating in the cytoplasm

Eukaryotic ribosomes

are 80S units with 40S and 60S subunits. Larger ribosomes. Ribosomes roam free in the cytoplasm, but they can also be bound to the exterior of the endoplasmic reticulum.

Growth factor analogs

are synthetic compounds that are structurally similar to growth factors but subtle differences do not allow them to function in the cell.

Daptomycin

forms pores in the bacterial cytoplasmic membrane

It is important for antimicrobial drugs used in vivo to exhibit selective toxicity. Elaborate on this statement explaining the meaning of selective toxicity.

Selective toxicity- is where antimicrobial drugs only inhibit or kill pathogens without adversely affecting the host. Both synthetic agents and antibiotics do this.

What bacterial genus is commonly associated with their ability to produce antibiotics?

Streptomyces sps.

Using sulfanilamide as an example, can you explain how bacterial growth is inhibited by growth factor analogs?

Sulfanilamide blocks the synthesis of folic acid (which is needed for nucleic acid synthesis) thereby inhibiting the growth of bacteria.

Describe all the cellular processes targeted by different groups of antibiotics in order to destroy bacterial cells that we discussed in class.

Targets of antibiotics: •Ribosomes •Cell wall •Cytoplasmic membrane •Lipid biosynthesis enzymes •DNA replication and transcription elements •Protein synthesis by disrupting translation

Mode of action of growth factor analogs

They kill cells by disrupting cell metabolism.

True/False - We have discovered certain strains of bacteria that have developed resistance to all known antibiotics.

True

Antibiotic resistance genes may be present either on the _________ or on a plasmid such as R plasmid.

bacterial chromosome

Reverse transcriptase inhibitors

block reverse transcriptase and production of viral DNA

Macrolides

inhibit protein synthesis by targeting the 50S subunit of ribosomes on a broad-spectrum.

Protease inhibitors

inhibit the processing of large viral proteins into individual components

Tetracyclines

inhibits protein synthesis by targeting the 30S subunit of ribosomes on a broad-spectrum.

Aminoglycosides

interfere with protein synthesis by targeting the 30S subunit of ribosomes

Platensimycin

interferes with lipid synthesis on a broad-spectrum

Neuraminidase inhibitors

interferes with viral release from host cells (successfully limit influenza infection)

Fusion inhibitors

prevent viruses from successfully fusing with the host cell

Interferons

small proteins that prevent viral multiplication by stimulating antiviral proteins in uninfected cells

Penicillin

targets cell wall synthesis by preventing cross-linking of peptidoglycan.

Quinolones are effective antimicrobial agents. They interfere with the activity of the enzyme DNA gyrase. What is the function of this enzyme in bacterial cells? So can you explain how quinolones work as antimicrobial agents?

DNA gyrase is needed to supercoil and package DNA inside the bacterial cell. Quinolones are effective against both Gram positive and Gram negative bacteria and is used to treat UTI's, Anthrax, Tuberculosis, and preventing respiratory diseases in animals.

How do microorganisms share resistance genes with other microorganisms?

Horizontal Gene Transfer The widespread use of antibiotics in medicine, veterinary medicine, and agriculture has provided favorable conditions for the spread of R plasmids with resistance genes.

How do broad spectrum antibiotics differ from narrow spectrum antibiotics? Give one example of each.

Narrow spectrum antibiotics like gram-positive bacteria and gram-negative bacteria vary in their sensitivity to antibiotics. Broad-spectrum antibiotics are effective against both groups of bacteria like Tetracycline.

What is the natural source (name the organism producing it) of the antibiotic penicillin? What is its mode of action?

Natural source of Penicillin is the fungus Penicillium chrysogenum. It targets the cell wall synthesis by preventing cross-linking of peptidoglycan.

What is the natural source of cephalosporins?

Natural source of cephalosporins is the fungus Cephalosporium sp.

What are nucleic acid base analogs and how do they work as antimicrobial agents?

Nucleic acid base analogs are formed by the addition of bromine or fluorine. They are used to treat viral and fungal infections and as a mutagen.

Pathogenic fungi can be more difficult to treat compared to bacteria. Suggest a possible reason for this statement.

Pathogenic fungi are harder to treat because they are eukaryotic and can't be treated through chemotherapy. The cellular machinery of fungi is for the most part the same as animals and humans, which means that the antifungal has to be topical. There are only a few drugs that can target the unique metabolic processes of fungi.

Describe resistance mechanisms seen in bacteria. How are some bacteria able to overcome the effects of antibiotics?

Resistance mechanisms: •Reduced permeability •Inactivation of antibiotic •Alteration of target •Development of resistant biochemical pathway •Efflux (pumping out of cell) Bacteria are able to overcome the effects of antibiotics by becoming antibiotic resistant through genetic encoding on either the bacterial chromosome or on the R plasmid.

Discuss why one antibiotic is not a sufficient weapon for destroying all bacterial cells.

Antibiotics are not sufficient weapons for destroying all bacterial cells because they differ based on the molecular structure, mode of action, and spectrum of antimicrobial activity. It also depends on the susceptibility of microbes to different antibiotics. Some gram-positive and gram-negative bacteria are sensitive to different antibiotics, and broad-spectrum antibiotics are effective against all types of bacteria. Each antibiotic targets different aspects like ribosomes, cell wall, cytoplasmic membrane, lipid biosynthesis enzymes, DNA replication and transcription elements, and protein synthesis by disrupting translation. Antibiotics are produced by several bacteria and fungi and due to antibiotic resistance, less than 1% of known antibiotics are clinically useful.

Why do antibiotics not destroy the cells in our (human) body?

Bacteria are prokaryotic and human cells are eukaryotic. When a particular antibiotic is designed or used against a bacteria, it targets a bacterial component or characteristic. Also, the antibiotics are target specific (selective) and those compounds won't go hunting down each cell they come across. Since those target components or characteristics are absent in a human cell, they are not going to be acted upon by the antibiotics and they survive. For example, penicillin is a beta lactam antibiotic and it targets the peptidoglycan cell wall. Due to the breaking of cell wall, followed by leaking of the cell components that particular cell dies. Now penicillin will work only when the target cell has peptidoglycan cell wall, otherwise it won't. So a human cell, which lacks peptidoglycan cell wall will remain unharmed.

What can we do to prevent the rapid rise in antibiotic resistance among bacteria? (Essay type question)

Do not take antibiotics for viral infections. Complete your prescribed course of treatment exactly as instructed by your healthcare provider. Do not stop taking your medicine even if you feel better, and do not save any antibiotics for future use. Do not take someone else's antibiotics because different kinds of antibiotics treat different types of bacterial infections. Use less antibiotics because the more antibiotics are used, the more resistant the bacteria can become because sensitive bacteria are killed, but stronger germs resist the treatment and grow and multiply. Repeated and improper use of antibiotics contributes to this process. According to the Guidelines for preventing antimicrobial drug resistance: -Vaccinate to prevent common diseases -Avoid unnecessary invasive procedures -Identify and target the pathogen -Treat with the oldest effective antimicrobial drug -Monitor antimicrobial use -Break the chain of contagion -Access experts

What are the processes that are targeted by antifungal drugs? Know the various categories we discussed.

Ergosterol inhibitors: target the unique fungal plasma membrane component ergosterol. Echinocandins: interfere with cell wall synthesis; inhibits 1,3 -D glucan synthase. Other drugs that target chitin biosynthesis, folate biosynthesis, nucleic acid synthesis, or disrupt microtubule aggregation.

Semisynthetic Penicillins are effective against Gram positive bacteria as well as ___

Gram-negative bacteria.

Penicillin G (natural) is primarily effective against ____ group of bacteria

Gram-positive

Look at the slide that shows a graph plotting antibiotic deployment and antibiotic resistance observed (Fig. from Nature Chemical Biology paper). Explain what this graph represents.

The graph represents the time it takes for microbes to become resistant to antibiotics from the time that the antibiotic was introduced to the public.