Question

Antibiotics are used to treat a wide variety of bacterial infections and have saved millions of lives since they were first introduced in the 1940s and 1950s. However, due to both overuse and misuse, many are no longer effective and The World Health Organisation (WHO) considers the emergence of new antibiotic-resistant bacteria to be a serious threat to global public health.

According to their mechanism of action, antibiotics can be divided into three main groups, those inhibiting cell wall synthesis, those inhibiting protein synthesis and those that inhibit nucleic acid synthesis. For example, penicillin and its related compounds prevent susceptible bacteria from creating a cell wall. They do this by binding to and inactivating an enzyme (transpeptidase) necessary for the cross-linking of peptidoglycan in the wall, thus stopping its formation. Resistance to this antibiotic is due to the bacteria producing its own enzyme called beta-lactamase which breaks the ring structure of the penicillin and prevents its ability to bind to the bacterial transpeptidase.

As with all proteins, beta-lactamase is encoded by a section of DNA – but how does that DNA and the ability to produce a new protein transfer from one population of bacteria that have resistance to another population that don’t?

Other than direct transfer from parent to daughter cell, horizontal transmission of DNA between different genomes also occurs. Horizontal gene transfer is made possible by the existence of mobile genetic elements, such as plasmids (extrachromosomal genetic material), transposons (“jumping genes”) and bacteria-infecting viruses (bacteriophages). These elements are transferred between organisms through different mechanisms, which in prokaryotes include transformation, conjugation, and transduction.

• Write a sentence for each of these mechanisms describing the manner in which the DNA can be transferred from one cell to another.

• Choose a disease or an organism that has a well-documented mechanism of resistance (such as methicillin resistant Staphylococcus aureus - MRSA or tuberculosis) and see if you can identify the gene or genes that confer resistance and the method of DNA transfer thought to contribute to its spread. This may be from one organism to another or may simply be passed down from mother to daughter cell due to environmental pressure.

• Finally, discuss the danger that antibiotic resistance poses in today’s society, consider how man has contributed to this and suggest any strategies that you think may be able to halt it or prevent its expansion

Answer 1

1.- Horizontal transfer mechanisms

- Plasmids (conjugation): Bacteria can give to each other plasmids, these are circular DNA molecules that can be expressed in the cell. When an antibiotic resistance gene is located in a plasmid, a cell can give the plasmid to another one by bridge-like connections

- Transposons: These are mobile genomic elements that can sometimes take some other fragments, like antibiotic resistance genes, and place them in another part of the genome. In some cases they can take these resistance genes and place them into plasmids, this allows for the bacteria to transfer such genes through plasmids

- Bacteriophagues (transduction): It is the process in which a virus transfers genetic material from one bacterial cell to another cell.

2.- Pathogen chosen: Carbapenem resistant Enterobacteriaceae

The gene responsable for this resistance is the one that produces the enzyme carbapenemase. Carbapenems are a type of antibiotic that also disrupts the cell wall synthesis pathway. Carbapenemase inhibits the activity of this antibiotic, thus providing the Enterobacteriaceae with resistance to this antibiotics

3.- Antibiotic resistance discussion

The abuse in the use of antibiotics has brought such wide spread antibiotic resistances through the process of selection. When a threat is widely applied to any organism population, the population be under strong selective pressure forces, being the most resistant individuals the ones that will most likely reproduce. This leads to the formation of a more resistant population, since the resistance is inheritable. We just made that with bacteria, applied a major threat to them using antibiotics, some of them had developed resistance (enzymes to inhibit the antibiotics), and such surviving individuals not only inherited the resistance, but they horizontally transfered the resistance too.

This brings more challenges to human health care, because it means many diseases that were known to be suceptible to certain treatments, are no longer able to be cured by the same means. Another consequence is that the further use of antibiotic treatments lead to worsen the situation. At the end of the day, this transforms into the endless coevolutionary "battle", where a species "fights" against the other to exploit their resource of interest, and this other species responds to defend its own interests. Pathogens against humans in this case.

The path to avoid further advancement in this situation is to regulate the use of antibiotics, and in some cases even follow alternative treatments that may lead to recovering without increasing the issue.