Antibiotic Resistance

Question 1

Superbug

Answer 1

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

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. Penicillinase (an enzyme that breaks down penicillin) was discovered in the natural bacterial population in samples that pre-date the use of therapeutic penicillin. In fact, a large portion of your microbiome is already resistant to antibiotics you have never been exposed to. How is that possible?

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. When there is HGT and rapid mutation working together, becomes very difficult to control.

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

Conjugation (transfer through pilus connection)

Question 9

Transduction

Answer 9

Transduction (transfer through bacterial virus, called a phage)

Question 10

Transformation

Answer 10

Transformation (direct uptake of DNA from outside the cell)

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.
   They are used and discarded for many other purposes. It is hard to get good numbers, but tons of chemical microbicides and antibiotics are dumped into the environment by pharmaceutical companies (primarily abroad) just because a batch was not up to standards.
2. There is also a dramatic overuse of antibiotics in the U.S. and internationally.
   It is estimated that 40-50% of patients with respiratory tract infections get antibiotics, although the vast majority are caused by viruses.
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). Thankfully this has been changing in recent years, though some farmers still give antibiotics deceptively or illegally. When animals consume antibiotics, they not only can develop resistance in themselves, but their fecal matter can contain bacteria with resistance genes, that are then spread over wide acres of land as fertilizer. The bacteria in the manure then trade plasmids with others in the soil, spreading resistance genes incredibly fast.

Question 12

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

Answer 12

Plans to mitigate the problem of antibiotic resistance include both 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.

Some researchers are trying to find ways to use bacteriophages (viruses that kill bacteria) to attack bacteria, which is a treatment approved in some other countries. Developing policies around antibiotic prescriptions, development of new antibiotics, use of antibiotics in agriculture and raising global awareness will also certainly be essential to mitigate and manage the problem of antibiotic resistance