Mastering Microbiology Chapter 20

Decreased permeability Drug inactivation Efflux pumps Altered drug target Two resistance mechanisms, altered drug target and drug inactivation, are general mechanisms that could be used against either drug A or drug B. The other two mechanisms listed, decreased permeability and efflux pumps, are only effective against drugs that have intracellular targets. Drug B, however, does appear to have an intracellular target—the cell's ribosomes. So while these latter two mechanisms wouldn't be effective against drug A, they could be effective against drug B. This means that all four mechanisms are possible for this doubly-resistant bacterial strain.

A Gram-positive bacterial strain is simultaneously treated with two different antimicrobials: Drug A, which targets a protein involved in cell wall synthesis, and Drug B, which targets ribosomes involved in translation. The bacteria continue to grow during the course of treatment, indicating resistance to both antimicrobials. What are all the possible resistance mechanisms this bacterial strain could have?

Antimicrobial X is less effective against the new shape of its target. The growth of bacteria in the presence of an antimicrobial means they are resistant to that antimicrobial. Bacteria can resist antimicrobial effects through a number of different mechanisms. In this case, the bacteria has altered the antimicrobial target itself, which prevents the antimicrobial from binding.

Antimicrobial X targets a specific protein in the cytoplasm of the bacterial cell, causing the bacteria to stop growing, but does not kill them. A few bacteria start to grow in the presence of antibiotic X. Analysis of the bacteria that can now grow shows that they have changed the shape of the target for antimicrobial X. What conclusion can be made?

True

Antiviral drugs target viral processes that occur during viral infection.

PABA

Bacteria that are resistant to sulfonamide have enzymes that have a greater affinity for what?

Altered porins in the cell wall block passage of antibiotic through the cell wall. A microbe develops a transport mechanism in the plasma membrane that rapidly pumps antibiotic out of the bacterial cell. An enzyme that destroys the antibiotic is produced. Target site is modified, so that an antibiotic is unable to bind to its target

Consider the different mechanisms through which antibiotics inhibit microbial growth, and consider what changes in the microbe might enable it to resist the inhibitory effects of antibiotics. Select all of the statements that describe a mechanism that would enable a microorganism to resist the action of an antibiotic. Target site is modified, so that an antibiotic is unable to bind to its target. An altered target enhances the binding of antibiotic. Altered porins in the cell wall block passage of antibiotic through the cell wall. An enzyme that destroys the antibiotic is produced. A transport mechanism that rapidly transports antibiotic through the plasma membrane into the cytoplasm is developed. A microbe develops a transport mechanism in the plasma membrane that rapidly pumps antibiotic out of the bacterial cell.

Resistant bacteria can have more efflux pumps, and can have less specific efflux pumps.

How might efflux pumps increase antibiotic resistance in bacteria?

Correct You have identified the statements that accurately describe the origins and spread of antibiotic resistance. It is important to understand that resistance typically originates through spontaneous mutations and then can spread horizontally through bacterial transformation, conjugation, and transduction and vertically through binary fission. Antibiotic use provides the selective pressure that reduces the number of antibiotic-susceptible bacteria, resulting in an increase in the number of antibiotic-resistant strains. Antibiotics don't cause the DNA changes that bring about the resistance, but rather provide a selective environment in which only those microbes that are resistant can proliferate. Antibiotic-resistance genes can be passed horizontally via transduction. Antibiotic resistance is readily transmitted to the next generation during binary fission. Mutations are the ultimate source of antibiotic-resistance genes. Antibiotic-resistance genes can be passed horizontally via bacterial conjugation. Antibiotics select for those microbes that have developed resistance, increasing their frequency in the bacterial population. Antibiotic-resistance genes can be passed from one bacterium to another by bacterial transformation.

Identify the statements below that accurately describe the mechanisms through which organisms acquire antibiotic resistance. Select all of the statements that accurately describe the origins and spread of antibiotic resistance. View Available Hint(s) Select all of the statements that accurately describe the origins and spread of antibiotic resistance. Antibiotics cause an increase in the rate of horizontal gene transfer. Antibiotic-resistance genes can be passed from one bacterium to another by bacterial transformation. Antibiotic-resistance genes can be passed horizontally via bacterial conjugation. Antibiotic resistance is readily transmitted to the next generation during binary fission. Antibiotics cause mutations; heavy antibiotic use directly leads to mutations in microbes, giving rise to antibiotic resistance. Antibiotics select for those microbes that have developed resistance, increasing their frequency in the bacterial population. Antibiotic-resistance genes can be passed horizontally via transduction. Mutations are the ultimate source of antibiotic-resistance genes.

streptomycin, isoniazid and ethambutol rifampin Correct Treatment of susceptible strains of M. tuberculosis typically includes a 6-month regimen of isoniazid, ethambutol, pyrasinamide, and rifampin. These are considered first-line drugs for the treatment of tuberculosis. If resistance develops, second-line alternatives, such as aminoglycosides, fluoroquinolones, and para-aminosalicylic acid (PAS) can be added to the regimen. In resistant strains, treatment is more difficult.

If Caleb's strain of M. tuberculosis is sensitive to antibiotic treatment, which of the following could be used to treat his infection? streptomycin penicillins and cephalosporins isoniazid and ethambutol rifampin

gram-positive bacteria

If penicillin G is chosen as the best treatment for a given infection, what microorganisms are most likely the cause?

Efflux pumps, beta-lactamases, and modification of porins all utilize membrane transport proteins.

Membrane transport proteins are required for which mode(s) of antibiotic resistance?

Streptomyces species

More than half of the antibiotics used today are produced by __________.

Drug inactivation via β-lactamases and altered target binding site Transpeptidase is a bacterial enzyme located outside the cell. Because of this, some resistance mechanisms, like decreased permeability and efflux pumps, are useless against antimicrobials (like penicillin) that target this enzyme. In contrast, directly inactivating penicillin via β-lactamases would be effective. In addition, altering the normal penicillin-binding site on transpeptidase would also be effective.

Penicillin's target is transpeptidase, a protein involved in cell wall synthesis. For a Gram-positive bacterium, which of the following mechanisms would be most effective in resisting penicillin's effects

DNA gyrase

Quinolones and fluoroquinolones act against what bacterial target?

bacterial conjugation.

R-plasmids are most likely acquired via bacterial conjugation. translation. transformation. transduction.

Antibiotic therapy is started with a broad-spectrum antibiotic because broad-spectrum antibiotics are effective against many gram-positive and many gram-negative bacteria. Correct. Azithromycin is a semisynthetic broad-spectrum antibiotic that can be used as an alternative to penicillin, is broader in range than erythromycin, and has better tissue penetration. Dr. Bell most likely assumes that the bacterium causing Caleb's infection will be susceptible to azithromycin and that this drug should clear the infection.

Review Caleb Bakersfield, a 42-year-old real estate agent, had just returned from a vacation to Russia. His childhood had been rough because of an alcoholic and abusive father, and Caleb had started his own drug addiction in his early teens. By his early twenties, he was addicted to heroin, lived on the streets, and frequently used dirty needles. In his thirties, Caleb joined a program to beat his addiction and to turn his life around. The trip to Russia was to celebrate a decade of being clean. Less than two months after his trip, Caleb started having respiratory complications, including a frequent cough and shortness of breath. He figured it was most likely a respiratory infection and made an appointment with his physician. After listening to Caleb's lungs, Dr. Bell determines that Caleb most likely has a lower respiratory infection and prescribes the antibiotic azithromycin. Dr. Bell reminds Caleb that it is important to complete his entire course of antibiotics, even if he feels better before he finishes all of the medicine. Dr. Bell also collects a sputum sample (mucus coughed up from the lower respiratory tract) and sends it to the laboratory for evaluation. Why does the physician start Caleb on the antibiotic azithromycin before laboratory results come back?

folic acid synthesis in bacteria Correct Sulfonamides are competitive inhibitors of one of the enzymes necessary for folic acid synthesis in bacteria

Sulfonamides interfere with __________. protein synthesis in fungi protein synthesis in helminths folic acid synthesis in bacteria anaerobic metabolism in protozoa

transduction.

The process of acquiring antibiotic resistance by means of bacteriophage activity is called

These antibiotics interfere with protein synthesis within eukaryotic mitochondria. Eukaryotic mitochondria have 70S ribosomes, composed of 50S and 30S subunits, which are very similar to the ribosomes of bacterial cells. Some of the antibiotics that target bacterial ribosomes will cause some toxicity in eukaryotic cells because of their effects on the mitochondrial ribosomes.

There are a large number of antibiotics that inhibit protein synthesis at 70S ribosomes found in bacterial cells but do not interfere with protein synthesis at the 80S ribosomes found in eukaryotic cells. Some of these antibiotics bind to the smaller ribosomal subunit and interfere with the reading of the mRNA code, whereas others bind to the larger ribosomal subunit and inhibit the formation of peptide bonds. Unfortunately, some of the antibiotics that inhibit protein synthesis in bacteria exhibit some toxicity to the eukaryotic host cells as well. What is the most likely reason for this toxicity to the host cell? Select the correct answer. These antibiotics interfere with DNA replication in eukaryotic cell nuclei. These antibiotics interfere with protein synthesis within eukaryotic mitochondria. These antibiotics plug up the membrane transport mechanisms in eukaryotic cells. These antibiotics bond to eukaryotic tRNA. These antibiotics bind to eukaryotic cytoplasmic ribosomes.

Chemotherapeutic agents should act against the pathogen and not the host.

What is meant by selective toxicity?

The bacterium is neither killed nor inhibited by the antibiotic.

What is meant when a bacterium is said to become "resistant" to an antibiotic?

the drug will kill or inhibit the growth of all of the sensitive bacterial cells

When a patient is treated with antibiotics, __________.

Penicillin

Which antibiotic is overcome by beta-lactamases? Which antibiotic is overcome by beta-lactamases? Tetracycline Sulfonamide Penicillin Tetracycline, Penicillin, and Sulfonamide are all affected by beta-lactamase.

Aminoglycosides and tetracyclines are inhibitors of protein synthesis. Sulfonamides inhibit the synthesis of essential metabolites. Correct Antibacterial drugs are often categorized by their mode of action against the target microbe. The following make up a short list of antibacterial drugs that are commonly used to treat infections. Penicillins (natural and semisynthetic) and cephalosporins are commonly used to inhibit synthesis of the cell wall. Chloramphenicol, aminoglycosides, tetracyclines, and macrolides are common inhibitors of protein synthesis. Polymyxin B and lipopeptides cause damage to the plasma membrane. Rifamycins and quinolones inhibit nucleic acid synthesis. Sulfonamides inhibit metabolic pathways. Combinations of these drugs can also be used to increase efficacy

Which of the following choices correctly matches the class of antibiotic and its mode of action? Aminoglycosides and tetracyclines are inhibitors of protein synthesis. Penicillins and cephalosporins inhibit nucleic acid synthesis. Sulfonamides inhibit the synthesis of essential metabolites. Lipopeptides inhibit cell wall synthesis.

Many individuals fail to complete their entire regimen of antibiotics. Some physicians prescribe the wrong medication, the wrong dosage, or the wrong length of time for treating tuberculosis. In many areas, tuberculosis antibiotics are unavailable or of poor quality. orrect One of the major reasons for drug resistance in M. tuberculosis is the length of antibiotic treatment. It is hard enough to get people to completely finish a course of antibiotics that lasts 7 to 10 days, let alone one that lasts 6 months. Individuals who begin treatment but do not finish only contribute to the resistance problem because the organisms they are harboring and transmitting to others are the ones resistant to treatment. Other factors that contribute to resistance include improper diagnosis and treatment, lack of drug availability, and poor quality of the antibiotics. With the increase in the number of organisms exhibiting resistance, researchers are now developing newer antimicrobials and revisiting ideas from before the antibiotic era.

Which of the following contribute to drug resistance in M. tuberculosis?

Silent mutation

Which of the following mutations would not result in antibiotic resistance? Which of the following mutations would not result in antibiotic resistance? Missense mutation Nonsense mutation Silent mutation Frameshift insertion Frameshift deletion

The Kirby-Bauer test is useful because it can differentiate bacteriostatic effects from bactericidal effects.

Which statement regarding tests for microbial susceptibility to chemotherapeutic agents is FALSE? View Available Hint(s) Which statement regarding tests for microbial susceptibility to chemotherapeutic agents is FALSE? The Kirby-Bauer test is useful because it can differentiate bacteriostatic effects from bactericidal effects. A broth dilution test is often used to determine MIC and MBC of an antimicrobial drug. During a disk-diffusion test, a clear zone around the test disk indicates that growth was inhibited. During the Kirby-Bauer test, a Petri plate with agar medium is uniformly inoculated with a standardized amount of a test organism.

Humans and other animal hosts lack peptidoglycan cell walls.

Why are chemotherapeutic agents that work on the peptidoglycan cell wall of bacteria a good choice of drug?

Dr. Bell prescribes Caleb HIV therapy because the virus is not affected by the antibiotics used to treat tuberculosis Correct HIV infections are caused by the human immunodeficiency virus, a RNA virus. Viruses are not susceptible to antibiotics; thus the treatment for Caleb's tuberculosis would be effective only against the bacterium, M. tuberculosis. Dr. Bell prescribes the HIV therapy and the antibiotics in order to help Caleb's immune system battle both infections. HIV therapy includes the use of antiretroviral drugs, nucleoside analogs, and nucleotide analogs such as HAART, zidovudine, and tenofovir, respectively. Newer HIV drugs are being created to inhibit viral entry into the cell and to prevent integration of the genome into host DNA. Often, HIV-infected individuals are given a "cocktail" of medications to treat the infection and to help combat antiviral resistance.

Why does Dr. Bell start Caleb on HIV therapy in addition to the antibiotics used to treat the tuberculosis? Dr. Bell prescribes Caleb extra medications to ensure a high enough dose to completely eliminate both pathogens. Dr. Bell prescribes Caleb HIV therapy because he does not think that Caleb will complete his regimen of antibiotics. Dr. Bell prescribes Caleb HIV therapy because the virus is not affected by the antibiotics used to treat tuberculosis. Dr. Bell prescribes Caleb HIV therapy because in conjunction with the antibiotics, it will eliminate the tuberculosis.

Viruses depend on the host cell's machinery, so it is hard to find a viral target that would leave the host cell unaffected.

Why is it difficult to find good chemotherapeutic agents against viruses?

Viruses use the host cell's processes to carry out their own reproduction

Why is it more difficult to treat viral infections than it is to treat bacterial infections?

It can also damage living human cell membranes, but the drug is safely used on the skin, where the outer layers of cells are dead.

Why is polymyxin only used on the skin?

Penicillin disrupts the cell wall, which is located outside of the cell membrane

Why would an efflux pump for penicillin located on a bacterial cell membrane not be effective at providing resistance to the drug?