Title: “Anti-evolvability drugs could slow antibiotic resistance in bacteria.”
Depiction of E. coli response to low doses of antibiotics causing sub-populations with different responses to emerge. Credit: John P Pribis
Publisher: Cell Press
Published: April 1st, 2019
Summary: Growing antibiotic resistance is a threat. Traditionally the focus is to develop new antibiotics. This article focuses on identifying a mechanism by which drug resistance forms and identify a drug that prevents the mechanism from developing antibiotic resistance. In this case researchers observed that low doses of ciprofloxacin (“DNA breaking” antibiotic) administered to E. coli caused a stress response in a fraction of the isolate population which resulted in high levels of reactive oxygen species (ROS) production. Which in turn, induced error prone DNA repair. This particular stress response strategy relies on a sort of mutation gambling that results in the rapid evolution of new antibiotic resistance without risking the entire microbial population. ROS-reducing drugs exist and are approved by the FDA for other uses. Researchers exposed E. coli to low dose ciprofloxacin and ROS-reducing drug edaravone in tandem and successfully prevented the formation of new antibiotic resistance in their tested E. coli populations.
Connection: Class covered how antibiotics treat bacterial infection. Bacteria develop antibiotic resistance for a variety of reasons as discussed in lecture. Antibiotic resistance prevention we discussed fuocused mainly at prevention of resistance development. Mechanisms by which resistance forms were also discussed but this idea to inhibit resistance mechanism during antibiotic treatment is quite clever.
Critical analysis: ScienceDaily is a reputable and credible news source. This story directly cites the original journal article and states its content is edited for “style and length”. This sort of reporting is perfect for casual scientific reading. It makes reading easy unlike reading the original journal article while staying completely factual and referenced. The perfect middle ground between deciphering a scientific journal article and reading a very watered down interpretation of the article in a non specialty news publication.
Question: What other mechanisms do bacteria use to develop antibiotic resistance? How could the mechanism you thought of be disrupted?
3 Comments for “A2: Microbes In The News-Antibiotic resistance and ROS treatment”
I agree with your critical analysis. From what I found to answer your question about other mechanisms of antibiotic resistance were that they develop the ability to enzymatically degrade the drugs, alter the bacterial proteins that are targeted by the drugs, or change the membrane permeability.
Response to Critical Analysis: I agree that ScienceDaily is a good source for casual scientific reading, and also appreciate that they provided a journal reference to the peer-reviewed article. I, myself, cringe to read the “edited for” declaration, but I see that it’s necessary for a more casual publication. I thought the at the Science Daily article focused more on the secondary finding that ROS-reducing agents reduced new antibiotic-resistant mutations, where the source article seemed more to stress the evolution of antibiotic resistance via two key factors: intracellular, inter-chromosomal reactions and the development of a mutation-prone sub-population. For me, I’d like to see more studies supporting this model, in addition to continued investigation into whether altering ROS presence consistently reduces bacterial mutagenesis without harming cells.
Question: Another common mechanism for antibiotic resistance is the action of efflux pumps, to move antibiotics out of cells to which they have gained entry. A substance which would either remove or incapacitate efflux pumps (for example, by “plugging” the pump with another substance with a similar conformation) might disrupt that mechanism.
This is such an important topic due to the increasing dangers of antibiotic resistant bacterium. The drug they developed, edaravone, seems very promising in helping slow down antibiotic resistance. This has a nice connection to what we were learning in class about horizontal gene transfer and how ROS increases this.