S1 - Antibiotic Resistance

Question 1

Superbug

Answer 1

When there are high morbidity and mortality due to a bacteria that has become resistant, it is often referred to as a superbug.

Extra info: Resistance to pharmacotherapy is not only an issue for bacteria, but it can arise in cancer cells, parasites, fungi, and other infections. Bacteria with acquired resistance include TB, S. aureus, Acinetobacter, E. coli, and V. cholera.

Question 2

Why mechanisms for resistance exist in nature

Answer 2

Microscopic organisms have been battling one another for millions of years by producing chemicals that can limit the growth of other organisms. Resistance to these chemicals has evolved in synchronization with them.

Mechanisms for resistance are therefore not new to human populations. They have been in development long before we ever started using antibiotics therapeutically. In fact, a large portion of your microbiome is already resistant to antibiotics you have never been exposed to.

(Example: Penicillinase was discovered in the natural bacterial population in samples that pre-date the use of therapeutic penicillin.)

Question 3

Horizontal gene transfer

Answer 3

When a bacteria takes up DNA from another source, it is called horizontal (or lateral) gene transfer (HGT)

Question 4

Genetic island/cassette

Answer 4

The part of a bacteria’s genome resulting from HGT is called a genomic island, or a genetic cassette. Genomic islands can confer resistance in the new bacteria.

Question 5

Vertical gene transfer

Answer 5

If a gene is inherited directly from a “parent” bacteria during reproduction, it is called vertical gene transfer (VGT).

Question 6

Intrinsic resistance

Answer 6

In the case of intrinsic resistance, no mutation is necessary to confer resistance. The bacteria simply overcomes the antibiotic by making more copies of the protein that the antibiotic targets.

Question 7

Ways in which resistance can develop (change drug target, modify cell walls, metabolize antibiotic, etc.)

Answer 7

It is important to note that resistance genes exist in bacteria with or without selection (does not “cost” them anything).

There are many different biological mechanisms by which they work. These include:

1. changing the shape of the antibiotics target protein,
2. developing the ability to metabolize the antibiotic,
3. developing the ability to recognize and actively pump out the antibiotic

Question 8

Conjugation

Answer 8

Transfer of genetic material from bacteria to bacteria through a sex pilus connection

Question 9

Transduction

Answer 9

Transfer of genetic material from bacteria to bacteria via a bacteriophage (Virus that infects bacteria)

Question 10

Transformation

Answer 10

Direct uptake of ‘spilled’ DNA from outside the bacterial cell into the bacteria

Question 11

The roles of humans in creating resistance

Answer 11

1. Less than ½ of the therapeutic antibiotics in existence are for human use.
2. There is a dramatic overprescription of antibiotics in the U.S. and internationally (Often for viral infections).
3. In agriculture, antibiotics are often used prophylactically because it was thought that they improve weight gain of animals (not to treat or prevent infection).

Question 12

What can be done to mitigate the problem of antibiotic resistance?

Answer 12

Identifying resistant bacteria earlier, and developing new methods for identifying antibiotics or other antimicrobial therapies.

For example, genotyping of strains in clinics to test for resistance is on its way to becoming common practice. Another common strategy is to use combinations of antibiotics, so that the bacteria is not able to acquire resistance. This is a method used often in the treatment of drug-resistant TB.