FR- Antibiotic resistance

Question 1

Give examples of antibiotic resistant bacteria (besides MRSA) that are of special concern

Answer 1

• Vancomycin resistant S. aureus (VRSA) strain which also resisted most other antibiotics, including ciprofloxacin, methicillin, and penicillin
• vancomycin-resistant enterococci (VRE) and a carbapenem-resistant Enterobacteriaceae (CRE) bacterium that caused deaths in a Los Angeles hospital in 2015

Question 2

What are the two types of resistance?

Answer 2

Inherent and acquired

Question 3

Give an example of inherent resistance

Answer 3

• The cell wall-less mycoplasma’s resistance to penicillin, which interferes with peptidoglycan synthesis.
• Similarly, many Gram-negative bacteria are unaffected by penicillin because it cannot penetrate the bacterial outer membrane

Question 4

When does acquired resistance occur?

Answer 4

Acquired resistance occurs when there is a change in the genome of a bacterium that converts it from one that is sensitive to an antibiotic to one that is now resistant

Question 5

Bacteria have evolved several resistance mechanisms: One is to modify the target of the antibiotic

Answer 5

This occurs by mutating a gene that functions in the synthesis of the target or by acquiring by HGT a gene that either encodes an alternative version of the target or encodes an enzyme that modifies the target.

This resistance mechanism is possible because each chemotherapeutic agent acts on a specific target enzyme or cellular structure.

Question 6

When does resistance to vancomyosin arise?

Answer 6

resistance to vancomycin arises when bacteria “pick up” the vanA gene that encodes a protein that changes the terminal d-alanine in the pentapeptide of peptidoglycan to either d-lactate or d-serine

Question 7

How can the affinity of ribosomes for erythromycin and chloramphenicol can be decreased?

Answer 7

By mutating the 23S rRNA to which they bind

Question 8

Antimetabolite action may be resisted through alteration of susceptible enzymes: Give an example

Answer 8

For example, in sulfonamide-resistant bacteria, the enzyme that uses p-aminobenzoic acid during folic acid synthesis often has a much lower affinity for sulfonamides

Question 9

A second resistance strategy is drug inactivation: Give an example

Answer 9

• The best-known example is hydrolysis of the b-lactam ring of penicillins by penicillinase and other b-lactamase enzymes.

Question 10

Drugs also are inactivated by the addition of chemical groups.

Give an example

Answer 10

• Chloramphenicol can be modified by the addition of acetyl-CoA to either of two hydroxyl groups.
• Aminoglycosides can be modified and inactivated by acetylation of amino groups and phosphorylation or adenylylation of hydroxyl groups present on the aminoglycoside

Question 11

The third resistance strategy minimizes the concentration of the antibiotic in the cell. How can this be accomplised?

Answer 11

This can be accomplished by altering membrane structure, particularly the outer membrane for Gram-negative bacteria, so that less antibiotic enters the cell

Question 12

Another approach is to pump the drug out of the cell after it has entered, how is this achieved?

Answer 12

• Using translocases, often called efflux pumps, that expel drugs
• Efflux pumps are relatively nonspecific and pump many different drugs; therefore, they often confer multidrugresistance.
• Many efflux pumps are drug/proton antiporters; that is, protons enter the cell as the drug leaves.

Question 13

Resistant bacteria may either use an alternate pathway to bypass the biochemical reaction inhibited by the agent or increase the production of the target metabolite. Give an example

Answer 13

• Some bacteria are resistant to sulfonamides simply because they use preformed folic acid from their surroundings, rather than synthesize it themselves.
• Other strains increase their rate of folic acid production and thus counteract sulfonamide inhibition. Again, these changes are most often mediated by HGT.

Question 14

What are immunity genes?

Answer 14

In antibiotic-producing microorganisms, the genes that encode resistance proteins are often referred to as immunity genes.

Question 15

True or false:

It is believed that many genes encoding antibiotic resistance in bacteria were “captured” from antibiotic-producing bacteria and moved by HGT to nonproducers, giving rise to a large pool of resistance-encoding genes outside the producing microorganisms

Answer 15

True

Question 16

Frequently a bacterial pathogen is drug resistant because it has a plasmid bearing one or more resistance genes; such plasmids are called:

Answer 16

R plasmids

Question 17

What do plasmid-borne resistance genes often code for?

Answer 17

enzymes that destroy or modify drugs

Question 18

Plasmid-associated genes been implicated in resistance to which antibiotics?

Answer 18

Aminoglycosides, chloramphenicol, penicillins, cephalosporins, erythromycin, tetracyclines, sulfonamides, and others

Question 19

How can a pathogen population can become resistant to several antibiotics simultaneously?

Answer 19

• Once a bacterial cell possesses an R plasmid, the plasmid (or its genes) may be transferred to other cells quite rapidly through HGT.
• Because a single plasmid may carry genes for resistance to several drugs, a pathogen population can become resistant to several antibiotics simultaneously, even though the infected patient is being treated with only one drug

Question 20

Can resistance genes be lost?

Answer 20

• Resistance genes can be lost if the bacteria are not consistently exposed to the antibiotic, and in some cases, to biocides and heavy metals.
• Thus, exposure to the antibiotic is a selective force that helps maintain the resistance gene in a population of bacteria
• . Of concern is the relatively low concentrations of antibiotics and heavy metals needed to maintain the carriage of resistance genes.
• In most cases, sublethal levels of 1% of the minimum inhibitory concentration (MIC) of a single antibiotic is sufficient to maintain the resistant phenotype.
• Unfortunately, the levels of antibiotic and heavy metal contamination in the environment far exceed this amount