Bitter-sweet resistance


Breaking down the microbiology world one bite at a time

Bitter-sweet resitance

A bacterial fairytale

Once upon a time, bacteria used to be afraid of antibiotics. Not long thereafter, they armed themselves with mutations. Because of these mutations, some bacteria were able to overcome the antibiotics. Life was easy for bacteria! Until today…

Researchers thought that the mechanism behind antibiotic resistance was simple: once the bacteria acquired mutations against an antibiotic, they could resist its life-threatening effects. They devised several methods to counter this problem. However, L. Galera Laporta and J. Garcia Ojalvo have found that antibiotic resistance may not be as simple a mechanism as understood by many. Bacteria can modulate their susceptibility to antibiotics by interacting with their neighboring bacteria. Hence, the counter-measures designed for antibiotic resistance may also not be so effective.

Antibiotic resistance: dynamic or classic?

Some bacteria are tolerant to one type of antibiotic, others to another type. When two bacteria with different degrees of tolerance to antibiotics are co-cultured in the presence of antibiotics, there could be four possible scenarios (Figure 1): (a) the tolerant bacteria survives, the sensitive bacteria dies; (b) both bacteria can survive because the tolerant bacteria makes enough neutralizing compound to help the sensitive bacteria fight against the antibiotic; (c) both bacteria die; (d) the tolerant bacteria dies, the sensitive bacteria survives by taking advantage of the tolerant bacteria’s ability to make neutralizing compounds.

Figure 1: Graphical representation of the bacterial response to antibiotics in single cultures and co-cultures. Image is taken from the article by L. Galera Laporta and J. Garcia Ojalvo

Ampicillin is a broad-spectrum antibiotic, meaning that it is effective against a wide range of bacteria. Researchers chose two bacteria with different susceptibility to ampicillin: Bacillus subtilis (B. subtilis) and Escherichia coli (E. coli). When grown along with the broad-spectrum antibiotic ampicillin, B. subtilis is tolerant and grows albeit a bit slow, but E. coli is sensitive and does not show optimal growth. Researchers found that when the two bacteria are grown together, B. subtilis loses its tolerance towards ampicillin whereas E. coli becomes tolerant to ampicillin and survives. So the fate of the co-culture followed the last route amongst the four scenarios explained in the previous paragraph.

Now, the audience will ask, “all the hype about antibiotic resistance has been around the mutations acquired by bacteria during evolution. How did the researchers reach this conclusion of dynamic antibiotic resistance?”  Researchers established single cultures of B. subtilis and E. coli with ampicillin as well as co-cultures. They extracted the supernatant from these cultures and grew fresh cultures of B. subtilis in the supernatant. They found that B. subtilis grew best in supernatant extracted from single cultures of B. subtilis, worse in supernatant extracted from co-cultures of B. subtilis and E. coli, and the worst in supernatant extracted from a single culture of E. coli (Figure 2).

Figure 2: (A) Cultures of B. subtilis, B. subtilis/E. coli and E. coli are grown in the presence of ampicillin. After 20 hours, the supernatant is used as media for independent new cultures of B. subtilis. Growth measurements are performed for the different cultures; (B) Change in bacterial growth (OD) over time for B. subtilis in the supernatant from the B. subtilis monoculture (blue line), the mixed culture (green line), and the E. coli monoculture (orange line). The dashed line corresponds to a culture of B. subtilis in the absence of antibiotics.

How would this new information impact medicine?

This dynamic interaction between microbes can be summarized as cooperator-cheater dynamics. The cooperator is B. subtilis because it neutralizes the antibiotic. The cheater is E. coli because it doesn’t contribute anything to inactivating the antibiotic and instead takes advantage of all the hard work done by B. subtilis. Laporta and Ojalvo mentioned in another interview that this information can be used to tweak antibiotic resistance of pathogenic bacteria, by providing probiotics containing non-pathogenic cheater bacteria. The presence of probiotic bacteria will make the pathogen sensitive to antibiotics, thus making it weak.

Does this mean that the physicians have to change the way they prescribe antibiotics? Tricky question! We may have to wait for a couple more years of research to find that out.

Link to the original post: L. Galera-Laporta and J. Garcia-Ojalvo, Antithetic population response to antibiotics in a polybacterial community, Science Advances, 6 march 2020
Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)

Featured image: Image created by the author

Other references:

1.      Özkaya Ö, Xavier KB, Dionisio F, Balbontín R. Maintenance of Microbial Cooperation Mediated by Public Goods in Single- and Multiple-Trait Scenarios. J Bacteriol. 2017 Nov 15;199(22):e00297-17.

2.      Katrina Krämer. Cheating bacterium becomes antibiotic-tolerant at expense of other species. Chemistry World 2020 March 10.