Chapter 10 Microbiology

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.

Aminoglycosides and tetracyclines are inhibitors of protein synthesis. Sulfonamides inhibit the synthesis of essential metabolites. 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.

Why does the physician start Caleb on the antibiotic azithromycin before laboratory results come back?

Antibiotic therapy is started with a broad-spectrum antibiotic because broad-spectrum antibiotics are effective against many gram-positive and many gram-negative bacteria. 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.

How does resistance to drugs spread in bacterial populations?

Both horizontal gene transfer and the growth of biofilms spread drug resistance.

What causes thrush?

Candida albicans Candida albicans causes thrush, especially in patients taking antibiotics. Antibiotics kill off the normal bacterial flora, and then the yeast can proliferate.

An antimicrobial that inhibits cell wall synthesis will result in which of the following?

Cells become more susceptible to osmotic pressure.

What is meant by selective toxicity?

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

Quinolones and fluoroquinolones act against what bacterial target?

DNA gyrase

What is DOT?

Directly Observed Therapy Mycobacterium tuberculosis is a very slow-growing organism. Therapy must continue for 6 to 12 months. Public Health officials are charged with making sure that all doses are administered on schedule for the duration of treatment.

Membrane transport proteins are required for which mode(s) of antibiotic resistance? Beta-lactamases Modification of a porins Efflux pumps, beta-lactamases, and modification of porins all utilize membrane transport proteins. Efflux pumps Modification of a metabolic enzyme

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

A side effect known as "black hairy tongue" may result from antifungal therapy.

False

Paul Ehrlich coined the term antibiotics for the "magic bullet" antimicrobials he pursued.

False

The outer membrane of Gram-negative bacteria enables many antimicrobial drugs to enter the cell more easily.

False

__________ cells would be expected to be the most susceptible to the action of polyene drugs such as amphotericin B, while __________ cells would be the least susceptible.

Fungal; bacterial

Broad-spectrum synthetic antimicrobials were discovered by

Gerhard Domagk.

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

Humans and other animal hosts lack peptidoglycan cell walls.

Why is polymyxin only used on the skin?

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 penicillin regarded as the first true antibiotic?

It is produced naturally by the fungus Penicillium.

Why do antimicrobial agents active against mycobacteria have to be administered for months or years rather than the typical 10-30 days prescribed to treat other infections?

Mycobacteria reproduce very slowly.

Label each figure with the class of antimicrobial that targets the ribosome to inhibit protein synthesis.

OXAZOLIDINONES block initiation. AMINOGLYCOSIDES change 30S subunit. ANTISENSE NUCLEIC ACIDS block ribosome attachment. CHLORAMPHENICOL inhibits bonding. LINCOSAMIDES and MACROLIDES block ribosome movement. TETRACYCLINES block tRNA docking.

The tRNA molecule holding a growing polypeptide chain is at the _____.

P site

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

PABA

Clavulanic acid could be used to protect which of the following antibiotics in a drug formulation?

Penicillin

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

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

If a particular bacterial species is resistant to beta-lactam antibiotics, which of the following might you expect to find inside the bacterial cells?

R plasmids

Ben's infection is treated with imipenem. A drug such as imipenem is chemically modified from penicillin. What are non-natural drugs developed from natural drugs called?

Semisynthetics Semisynthetics are chemically altered antibiotics that are more effective, longer lasting, and easier to administer.

Which of the following is a primary advantage of semisynthetic drugs?

They have a broader spectrum of action.

An antimicrobial drug that blocks the transport of NAG and NAM from the cytoplasm is targeting which of the following cellular processes?

cell wall synthesis

Drug-resistant populations of microbes arise when

exposure to drugs selectively kills sensitive cells, allowing overgrowth of resistant cells.

A medication that inhibits synthesis of ergosterol would be effective in treating

fungal infections.

Macrolides inhibit protein synthesis by blocking (catalysis/binding/movement) of the ribosome.

movement

Ribavirin is an antiviral that interferes with

nucleic acid synthesis.

Which of the following is NOT a possible side effect of antimicrobial therapy? disruption of normal microbiota toxicity allergies resistance

resistance Antimicrobial therapy does not cause resistance as a side effect of treatment.

An antimicrobial disk on a Kirby-Bauer plate that shows no zone of inhibition indicates that the microbe being tested is __________ to the drug.

resistant

Bacterial DNA replication requires the enzyme gyrase, but eukaryotic replication does not. Ciprofloxacin ("Cipro") inhibits gyrase activity. This is an example of

selective toxicity

Which of the following pathways is specifically inhibited by trimethoprim?

the conversion of dihydrofolic acid to tetrahydrofolic acid

The β-lactams are narrow spectrum antibacterials because

the outer membrane prevents their entry into cells.

The action of some antivirals prevent (attachment/synthesis/uncoating), an event shortly after entry of the virus into the cell.

uncoating

One aspect that must be evaluated during the development phase is the interaction of your drug with the host (i.e., what effect will the drug have on human cells?). There are several important factors to consider in this interaction, including the selective toxicity of your potential drug. Which of the following statements most accurately describes the principle of selective toxicity?

Selective toxicity refers to the ability of an antimicrobial to kill microbes with minimal damage to the host. Your studies using both in vitro and in vivo models indicate that your drug has a high selective toxicity. This means that it is effectively toxic against bacterial pathogens while having minimal toxic effects on the host (eukaryotic) cells.

Which of the following mutations would not result in antibiotic resistance?

Silent mutation

What is a superinfection?

Superinfection is a disease caused by an organism that is often an opportunist or one that was present in low numbers. Superinfection is a sequel to removal of the normal flora by antibiotic treatment. Removal of the normal flora allows opportunists that are normally present in low numbers to proliferate and produce disease.

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

The bacterium is neither killed nor inhibited by the antibiotic.

Why do the beta-lactam drugs affect bacteria but not human cells?

The beta-lactam antibiotics act on bacterial cell walls; human cells do not have cell walls. Beta-lactams prevent NAM subunit cross-linkages affecting the peptidoglycan layer of the Gram-positive cell wall. Human cells do not have cell walls; therefore, beta-lactam drugs do not affect them.

Typically beta-lactam drugs affect the peptidoglycan layer on bacteria. Why would beta-lactam drugs typically be considered more active against Gram-positive bacteria and less so against Gram-negative bacteria?

The cell walls of Gram-positive bacteria have a thick peptidoglycan component. The damage from beta-lactam action affects a greater proportion of the Gram-positive cell walls than Gram-negative cell walls.

If the patient were to get a subsequent urinary tract infection, what should the doctor prescribe knowing that she is susceptible to thrush?

The doctor should prescribe an antibiotic specific for the bacterial species causing the urinary infection. By using an antibiotic specific for the bacterial species causing the infection it will increase the chances of the remaining normal flora still being present to counter any secondary infections.

R-plasmids are extrachromosomal DNAs that contain genes for antimicrobial resistance.

True

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

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

Which category of antimicrobial drug works by changing the shape of a ribosome?

aminoglycosides An aminoglycoside changes the shape of a 30S subunit causing the ribosome to misread the mRNA.

Which antimicrobial drugs affect the structure of the ribosome itself?

aminoglycosides, antisense nucleic acids, and oxazolidinones Each of these drugs actually modifies or prevents the formation of the complete 70S ribosome.

Which of the following antibiotics disrupts cytoplasmic membrane function?

amphotericin B

Nucleotide or nucleoside (analogs/antisense/acids) are antimicrobial agents that mimic the chemical structure of DNA building blocks.

analogs

Competition between beneficial microbes and potential pathogens is called microbial (synergy/antagonism).

antagonism

Drugs that slow bacterial growth would be (competitive/synergistic/antagonistic) to penicillin.

antagonistic

Synthetic antimicrobials that block protein synthesis by binding to the mRNA are

antisense nucleic acids

Which category of drug is complementary to mRNA of the pathogen?

antisense nucleic acids The antisense nucleic acids are composed of the same nucleotide bases and are complementary to the mRNA.

The most limited group of antimicrobial agents is the ________ drugs.

antiviral

Beta-lactam antibiotics have an effect on which of the following types of cells?

bacterial cells

R-plasmids are most likely acquired via

bacterial conjugation

A (bacteriostatic/bacteriocidal/minimum) concentration of a drug is one at which microbes survive but are not able to grow and reproduce.

bacteriostatic

Why is the drug actinomycin used only in research applications or in the treatment of cancer?

because it is active against both prokaryotic and eukaryotic cells

Why do antimicrobial agents active against mycobacteria have to be administered for months or years?

because mycobacteria reproduce very slowly

Which of the following can result when antibiotic therapy disrupts the normal microbiota?

both pseudomembranous colitis and thrush

Infection of the ________ would be the hardest to treat with antimicrobial drugs.

brain

How did the multi-drug-resistant strains of Mycobacterium tuberculosis, like those in the prison, arise?

conjugation and exchange of resistance factors located on plasmids Horizontal gene transfer of plasmid resistance factors is one highly effective method of spreading multi-drug-resistant strains throughout hospitals and prisons.

A new antibacterial medication prevents the assembly of ribosomes on mRNA. The new medication would be

either an antisense RNA or a type of oxazolidinone.

Which of the following antimicrobial drugs would likely be useful to treat a staphylococcal infection?

erythromycin

Most broad-spectrum antibiotics act by

inhibiting protein synthesis.

The mechanism of action of the antibiotic vancomycin is

inhibition of cell wall synthesis.

Which of the following is NOT a direct mode of action of antimicrobial drugs? inhibition of nucleic acid synthesis inhibition of cell wall synthesis inhibition of flagella formation inhibition of protein synthesis

inhibition of flagella formation

Which of the following is NOT a direct mode of action of antimicrobial drugs? inhibition of protein synthesis inhibition of cell wall synthesis inhibition of nucleic acid synthesis inhibition of flagella formation

inhibition of flagella formation

Which of the following is NOT a type of side effect exhibited by antimicrobial drugs? disruption of normal microbiota inhibition of host cellular enzymes allergic reactions damage to liver or kidney tissue

inhibition of host cellular enzymes

The mechanism of action of erythromycin is

inhibition of protein synthesis.

A medication which specifically targets cell walls that contain arabinogalactan-mycolic acid is

isoniazid.

Which category of antimicrobial drug essentially acts to stall a ribosome as it reads mRNA?

macrolides Macrolides block the movement of a ribosome along mRNA, so the E site is never emptied and polypeptide formation is stopped.

One approach that is becoming more common in drug D&D is to search for antimicrobial-producing organisms in relatively pristine environments. A pristine environment is one that has been relatively unperturbed by humans and/or domestic animals. Your D&D team is searching for novel antimicrobials produced by bacteria in a remote area of a temperate rainforest in the Pacific Northwest. Which of the following terms would accurately describe your drug? natural antibiotic synthetic chemotherapeutic agent semisynthetic

natural antibiotic chemotherapeutic agent You have found bacteria that demonstrate antimicrobial activity in early testing. D&D chemists on your team have successfully extracted and purified the natural antibiotic from the bacteria. Your focus now turns to microbiological evaluation of the compound.

Which antibiotic is overcome by beta-lactamases?

penicillin

Most drugs that inhibit the synthesis of the cell wall act by

preventing the cross-linkage of NAM subunits.

Chloramphenicol blocks the action of the large (50S) subunit. This essentially _____.

prevents the formation of peptide bonds Without the formation of peptide bonds, amino acids diffuse away and protein synthesis ceases.

The majority of broad spectrum antibacterial medications inhibit (DNA/protein/RNA) synthesis.

protein

Inhibiters of DNA synthesis specifically effective on prokaryotes are

quinolones.

A sulfonamide and trimethoprim may be administered in combination to

reduce development of antibiotic resistance.

Second-generation drugs are semisynthetic drugs developed to combat (immunity/resistance) against an existing drug.

resistance

Which drug for the treatment of tuberculosis inhibits RNA production and colors body secretions red-orange?

rifampin Rifampin directly inhibits transcription and imparts a red-orange color to body secretions.

A compound is extracted from a microbial culture and is modified in the laboratory for use as an oral medication. This product would be a(n)

semisynthetic antimicrobial.

A particular microbe gains resistance to gentamicin. You might also expect this microbe to exhibit resistance against __________.

streptomycin

Which of the following is NOT associated with the work of Paul Ehrlich? arsenic compounds the concept of chemotherapy the concept of the "magic bullet" sulfanilamide

sulfanilamide

Which of the following molecules would inhibit the biosynthetic pathway that leads to the formation of DNA and RNA?

sulfonamide In this biosynthetic pathway, dihydrofolic acid is enzymatically produced from PABA. This is blocked by sulfonamide.

A compound is structurally similar to PABA and inhibits folic acid synthesis. It is most likely a(n)

sulfonamide.

Medications which should NOT be prescribed for a pregnant woman include penicillins. sulfonamides. tetracyclines. aminoglycosides. sulfonamides and tetracyclines.

sulfonamides and tetracyclines.

Secondary infections that result from the killing of some of the normal microbiota are called (antagonism/superinfections/resistance).

superinfections

The cooperative activity of drugs such as beta-lactam antibiotics and clavulanic acid, a β-lactamase inhibitor, is known as

synergism.

Which of the following activities can be shown to increase resistance among microbial populations?

taking antibacterial drugs for viral infections

What is microbial antagonism?

the ability of the normal flora to outcompete and outgrow pathogens Normal flora is well adapted to its niche. These bacteria may utilize nutrients more quickly or produce bacteriocins that inhibit growth of other microbes.

What is the therapeutic index?

the drug dose the patient can tolerate divided by the effective dose The therapeutic index is the drug dose tolerated by the patient divided by the effective dose.

When a patient is treated with antibiotics, __________.

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

Antimicrobial drugs are selectively toxic. This means _____.

the drugs are more toxic to the pathogens than to the patient They selectively target physiological and anatomical differences between pathogens and patients.

External infections can be treated by (surface/topical) administration, in which a drug is applied directly to the site of infection.

topical

Selective (toxicity/action/treatment) means that a given antimicrobial agent is more toxic to a pathogen than to the host being treated.

toxicity

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

transduction

Who was the most likely source of infection for this child?

uncle The child most likely had direct contact with her uncle.

Which of the following is NOT a beta-lactam antibiotic? vancomycin penicillin G methicillin cephalothin

vancomycin

The first synthetic antimicrobial widely available for treatment of infections

was an antimetabolite.

Which of the following classifications would best describe Candida albicans?

yeast Candida albicans is a unicellular chemoheterotroph that has a nucleus.

Prokaryotes contain _____ ribosomes.

70S 70S ribosome of prokaryotes is composed of smaller 50S and 30S subunits.

If the MBC for a particular drug is 16 µg/ml, which of the following serial dilutions of the drug is likely to be the MIC?

8 µg/ml If 16 µg/ml is a bactericidal concentration of the drug, then a bacteriostatic concentration (reflected by the MIC value) would be expected to be lower. Typically, it would be the next lowest concentration of the drug in the serial dilutions being tested.

In order to gain FDA approval for your drug, you must elucidate its mechanism of action (MOA). MOA refers to the particular pathway/ process/molecule that will directly be impacted by your drug. Current antibiotic therapies against bacterial infection use one of five characterized mechanisms.

Inhibition of cell wall synthesis: penicillin Inhibition of: streptomycin Disruption of cytoplasmic membrane: gramicidin Inhibition of general: sulfanilomide Inhibition of DNA or RAN synthesis: trifluridine Your testing has revealed that your drug has direct effects on the cytoplasmic membrane of bacterial cells. In collaboration with a biochemist on your team, you continue characterization of your molecule and its mechanism of action and determine that it is a small peptide molecule that forms a series of pores or channels in the membranes of bacterial cells.

In a broth dilution test, the first clear tube in the dilution series indicates which of the following?

MIC

The abbreviation (MIC/MID/MBC) stands for the smallest amount of a drug that will inhibit the growth and reproduction of a pathogen.

MIC

How might efflux pumps increase antibiotic resistance in bacteria?

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

While in the development phase, you are also required to determine both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for your drug. While these values directly relate to the efficacy of the drug against bacteria, they will also be informative for the next stages of development, which include studies to determine effective dosages within a host. The picture depicts the results of an MBC test. Based on these data, the MIC for your drug would be __________ and the MBC would be __________.

8 μg/ml; 16 μg/ml You have completed some of the important initial steps necessary in the development of a new antibiotic. From here, more extensive testing will be required to determine the effectiveness in a eukaryotic host. Experiments will also need to be conducted in order to determine safe and effective dosage and delivery. While this activity has highlighted some of the important steps taken during the discovery and development of a new antibiotic, it is important to realize that this is a time- and funding-intensive process. In reality, new antibiotic discovery and development can take decades and cost millions of dollars.

Disruption of the normal microbiota can result in infections caused by which of the following microbes?

Candida albicans, Mycobacterium, and Clostridium difficile

The project that you are working on was initiated in response to the growing threat of antibiotic resistance in both hospital and community settings. Even in the early discovery and development phase, it is important to think ahead to try to minimize the likelihood that bacteria will be able to evolve resistance to your new drug. Understanding how resistance emerges is an essential part of this process. Which of the following statements is NOT true regarding the evolution of antibiotic resistance in bacteria?

The exposure of bacteria to an antibiotic causes the bacteria to produce resistance genes. In the absence of a selective pressure, such as a certain drug, bacteria that possess genes that confer antibiotic resistance will reproduce more slowly due to the energy expense of maintaining resistance genes. In the presence of a selective pressure, however, the sensitive bacteria will be killed and the bacteria that possess genes that confer antibiotic resistance will have a reproductive advantage. Therefore, over time the genes for resistance will increase in frequency within the population.