Tag Archives: evolution of antibiotic resistance

Plasmids and Team Players

Let’s say you have a problem at your hospital with carbapenemases.

One of the obvious solutions would be to reduce the use of carbapenems in order to reduce the selection pressure.

However even if you stopped carbapenem usage altogether the carbapenemases would not necessarily disappear…

This is because carbapenemases are often plasmid borne, and there are often antibiotic resistance genes for other antibiotics, e.g. A, B & C sitting on the same plasmid.

As long as the (high) usage of antibiotics A, B & C continued then the selection pressure would favour plasmid retention in the bacterium, and thus allowing persistence of the carbapenemase.

Selection pressure by proxy.

Are we all doomed?

Not necessarily…

A gene expressing one antimicrobial resistance determinant comes at an energy cost to a bacterial cell. Plasmids expressing multiple resistance genes come at even more energy cost to the cell. You can be sure if it did not need the plasmid to ensure its survival, it would be mercilessly dumped, and probably sooner rather than later.

Therefore even a modest reduction in carbapenem usage, along with a reduction in antibiotics A, B & C may go a long way to solving your problem.

Advances in molecular methods and whole genome sequencing over the next decade will mean that it will become much easier to work out exactly which resistance genes are contained in the plasmids circulating in our local hospitals, and anti-microbial stewardship can thus be optimised accordingly.

Sounds space age?

Not really, we just need to be aware that resistant bacteria are very smart in an evolutionary sense, and we need to stay alert, and not give them the niches they are looking for…

Michael

Illustration courtesy of www.biologyfun.blogspot.co.nz

“Open and Closed”

Staphylococcus_aureus_jpeg

Will Staphylococcus aureus ever become completely resistant to penicillin?

At present about 10% of Staphylococcus aureus isolates worldwide retain susceptibility to penicillin. It has been like this for many years. The reason for this is probably two-fold.

  1. Bacterial populations do not exist in a closed system. Therefore they can “escape” to places where there is no selection pressure.
  2. The acquisition of resistant determinants by a bacterium almost always (if not always) comes with a fitness cost. Thus in the absence of any selection pressure, the resistant strain is unlikely to become dominant in such a hypothetical setting.

I would be very worried if Staphylococcus aureus as a population became completely resistant to penicillin, but I don’t think it will happen, not in “real time” anyway. On a population basis, I am not aware of any bacterial species which has variable resistance to an antibiotic, which has then become completely resistant to an antibiotic due to the use of that antibiotic in the population.

People worry about individual bacterial isolates being resistant to all known antibiotic classes, and label it as “The end of the antibiotic era”, which of course it is in a sense, and obviously terrible for the individual patients involved. But as microbiologists, I believe we need to be thinking about resistance much more in terms of bacterial populations, because this is where the answers to future resistance rates and the evolution of resistance really lie….

Michael