Can antibiotic-resistant bacteria strains lose their resistance over generations, if they stop being exposed to the antibiotic?

Submitted by enjrolas t3_zni9cx in askscience

There's lots in the news about antibiotic-resistant bacteria, and I'm trying to get a more nuanced understanding of how bacteria develop resistance, and if they ever lose that resistance over time. I know that, in the world of genetically engineered bacteria, it's hard to keep a trait stable over many generations of bacteria. If the trait isn't necessary for the bacteria's survival, it often mutates away. Genetic engineers often tie interesting traits to a separate trait for bacterial resistance, and then expose the bacteria to antibiotics to select (in theory) for just the bacteria that have an intact version of the special trait and the associated resistance.

I'm curious about what happens if you take a bacteria strain, like MRSA, that has evolved a resistance to drugs in the methicillin family, and then culture it in an environment where it's not exposed to any antibiotics. Does the bacteria lose the resistance over generations? How long does it take? If the culture loses resistance over time, and then you expose the culture to methicillin again, does the culture re-gain resistance faster, than, say, a naive strain of S. aureus that's never developed resistance in the first place? Is inherited resistance forever, or does it require continued exposure to antibiotics to maintain that resistance?

Also, got any recommendations for good books about bacterial resistance?

30

Comments

You must log in or register to comment.

demachy t1_j0j8vaj wrote

The resistance will eventually be lost. The rate of loss will depend on the initial genetic diversity, mutation rate, reproduction rate, and other evolutionary forces (e.g. what resources are limitted). I don't know a book off hand, but these are all evolutionary genetics questions. I'm sure an introductory text in evolutionary genetics or population genetics will contain most of the answers you're looking for (tip: you don't need the latest version ($$$), anything published in the last ten years will do)

16

demachy t1_j0j900w wrote

Oh, and recombination rates, but bacteria are particularly sneaky with horizontal gene transfer

3

PerspectivePure2169 t1_j0jo2ew wrote

There are many parallels between drug resistant bacteria and herbicide resistant weeds, including population numbers and how resistance is gained and lost.

Since there isn't parallel gene flow in weeds, the answer hinges upon the question "does the resistance trait put the organism at a competitive disadvantage in the absence of the herbicide?"

If the answer is no, then the trait will persist for many generations, because there's no cost to keeping it, and plants like to keep many genetic pathways for handling threats - that's why their genome dwarfs ours.

If the answer is yes, then the trait will diminish at a rate dependent on how much a competitive disadvantage it puts them at relative to weeds without the trait.

So if it affects their water efficiency in a dry climate- it's going away quickly. But if the cost is minor, it will last longer.

12

goatbears t1_j0kijcz wrote

If the bacteria are in a competitive environment, they will quickly lose resistance because DNA replication and protein production takes energy and time. So they will replicate slightly slower than bacteria without the added metabolic load.

If the resistance gene is on a plasmid it will likely lose it and selection will likely pick the bacteria without the added metabolic load of keeping a useless plasmid around. In this case it will take just as long to develop resistance as the first time (until it captures DNA with the antibiotic resistance on it).

If it has integrated into the chromosomal DNA, it will likely randomly mutate a few nucleotides to limit the amount of energy spent producing the protein. But the extra DNA will likely not cause enough of a difference in metabolic load to make them uncompetitive. This will allow them to regenerate the antibiotic resistance much faster than they did initially because they only have to randomly mutate a few nucleotides to get back their resistance

4

perta1234 t1_j0lwm3q wrote

This is from Seppälä and colleagues 97 "Consumption of macrolide antibiotics decreased from 2.40 defined daily doses per 1000 inhabitants per day in 1991 to 1.38 in 1992 (P = 0.007) and remained near the lower level during the study period. The change in consumption was followed by a steady decrease in the frequency of erythromycin resistance among group A streptococcal isolates from throat swabs and pus samples, from 16.5 percent in 1992 to 8.6 percent in 1996 (odds ratio for 1996 as compared with 1992, 0.5; 95 percent confidence interval, 0.4 to 0.5)."

1

OuiLePain69 t1_j0obr29 wrote

Acquired resistance will be lost over time, but different bacteria have natural resistance to some antibiotics types that are inherent to their basic metabolism and will persist forever. For example, Mycoplasma pneumoniae has no cell wall and therefore will always be resistant to beta-lactamins.

1