Bacterial exposure to ZnO nanoparticles facilitates horizontal transfer of antibiotic resistance genes
Xiaolong Wang, Fengxia Yang, Jing Zhao, Yan Xu, Daqing Mao, Xiao Zhu, Yi Luo, P. J. J. Alvarez
All old news, and yet still strikingly terrifying; each year, more than 23,000 Americans die as a result of infections from antibiotic-resistant bacteria. A recent CDC report hasn’t alleviated many fears, either: in 2017, lab tests detected unusual antibiotic-resistant genes in bacteria throughout the United States.
Meet carbapenem-resistant Enterobacteriaceae (see Figure 1). Infection with these bacteria kills up to half of infected patients. They are resistant to all or nearly all of the antibiotics we have today.
Figure 1. Not to be confused with purple packing peanuts. Source: Centers for Disease Control and Prevention.
Antibiotics and antibiotic resistance is often compared to an arms race. As we develop better drugs to attack disease-causing germs, bacteria develop ways around the effects of the drugs, new and old. It’s remarkable evolution in real-time, with real consequences.
Scientists studying antibiotic resistance look at how bacteria develop this resistance. Bacterial resistance is encoded in genes, just like the ones you and I have. Bacteria can share resistance genes with each other or pick them up from their environment; resistance genes have been found floating around in seawater, marine sediments, agricultural drainage, soils, and biofilms.
A recent paper from Nankai University showed that human activity affects gene transfer, too. Specifically, our use of nanoparticles.
What’s Nano got to do with it?
Nanotechnology is another hot-topic-science-buzzword, for good reason- many materials have dramatically different properties at this oh-so-small scale. A sheet of paper, for example, is 100,000 nanometers thick. (Check out a cool graphic from the National Nanotechnology Initiative here). The mania seems to have died down a bit, but not before we incorporated nanotechnology into a ton of consumer products: fabrics, skin care products, batteries, sporting goods (tennis balls and racquets, golf clubs), medicines, and electronics.
One commonly used material is zinc oxide nanoparticles. You may remember the classic life guard archetype, sporting a white nose from the very same stuff; now, sunscreen is commonly made with zinc oxide in nanoparticle form. Zinc oxide nanoparticles also have made their way into other cosmetics and applications in the chemical industry.
Figure 2. The old-school zinc oxide was more paste than lotion. Source: Caddyshack.
The more applications a chemical has, the more likely it’ll make it into the environment. As a result, zinc oxide nanoparticles have a high potential for contaminating the environment.
Once out in the world, though, what might the consequences be? There has been research on the effects of what exposure to high levels of nano-zinc oxide does to bacteria (answer: it really stresses out the bacteria and damages their cell walls), but that doesn’t reveal too much about what might happen at environmentally relevant levels of nano-zinc oxide. Often, it makes sense to study the impact of high concentrations of potentially toxic chemicals in a lab setting, to ensure you can observe the effects. But these concentrations are frequently much higher than what we might observe out in the world.
Here is where we circle back to our big question: what happens if we have nano-zinc oxide in our environment, along with the bacteria and the resistance gene floating around?
How to build a superbug
Wang et al designed experiments studying mixtures of nano-zinc oxide at low concentrations, plasmids (resistance genes), and bacteria. They gave the bacteria fluorescent green tags, and the plasmid fluorescent red tags, and took pictures of the growing bacteria before and after adding the plasmid (see Figure 3).
You can observe in the first row of images of before the plasmid was added that no red tags are visible, only the green. In the second row, the final picture (labeled Merged) shows that the bodies are both red and green, indicating that the bacteria (green) absorbed the plasmids (red).
Figure 3: Bottom row, far right: no red bodies without green, and vice versa, indicating that the bacteria took up all of the plasmids available. Source: Wang et al. 2018.
With further testing, they were able to discover the mechanism. The nano-zinc oxide particles attacked the cell walls of the bacteria but didn’t damage them enough to kill the bacteria. The attacks did, however, put holes in the walls, allowing for the cells to take up the floating resistance gene easily (see Figure 4).
Figure 4. How bacteria can take up plasmids through holes in their cell walls created by nano-zinc oxide. The altered bacteria are called transformants. Source: Wang et al. 2018.
It turns out, too, that the form of zinc matters; with only zinc around, no effect was observed, indicating it’s not enough to have normal zinc present. The nanoparticle size is key.
I ain’t got no crystal ball
As we continue to develop and nanotechnology products in our everyday lives, it’s important that we recognize potential effects downstream. It’s not just your lotion or your t-shirt; everything eventually ends up in our waterways, and we need to be responsible stewards. Not just for the environment’s sake, but for ours– antibacterial resistance is no joke.
About Antimicrobial Resistance, The Centers for Disease Control and Prevention
What is Nanotechnology?, The National Nanotechnology Initiative