In the pursuit of beautifully blemish-free skin, many of us may go off the beaten path, spraying a zit with Windex (thanks, My Big Fat Greek Wedding) or the pricer option of slinging 24 karats of gold (yes, actual gold) on our faces. We don’t recommend either of these. A more recent trend has folks microdosing on Accutane, also known as isotretinoin, an oral acne medication that isn’t without serious side effects.
But for those preferring something a bit more avant-garde, researchers in Europe have engineered a “smart” bacteria capable of producing acne-fighting chemicals.
Called Cutibacterium acnes, this bacteria is normally found colonizing our skin, predominantly in areas rich with sebaceous (or oil-producing) glands. While it’s an opportunistic pathogen that doesn’t take kindly to having its genome altered, scientists figured out a way to get the bacteria to produce a molecule called neutrophil gelatinase-associated lipocalin (NGAL), which controls sebum production. Scientists validated this ability in experiments with sebaceous cells in Petri dishes and then applied the bacteria to the skin of mice.
The findings were published this week in the journal Nature Biotechnology.
“We have developed a topical therapy with a targeted approach, using what nature already has. We engineered a bacterium that lives in the skin and make it produce what our skin needs,” Nastassia Knödlseder, the study’s first author and a postdoctoral researcher at the Universitat Pompeu Fabra in Spain, said in a press release. “Here, we focused on treating acne, but this platform can be extended to several other indications.”
While sebum produced by sebaceous glands keeps the skin moist, it can plug up hair follicles and cause acne when it mixes with dead skin cells and bacteria. Broad-spectrum antibiotics are often prescribed for severe cases of acne; however, because these drugs can’t discriminate between good and bad microbes, this can lead to harmfully disrupting the skin microbiome.
On the other hand, Accutane, a form of vitamin A, culls sebum-producing skin cells (called sebocytes) by increasing levels of NGAL on the skin. Some studies indicate that the drug may help promote a more beneficial skin microbiome. Yet, a problem with Accutane is that it comes with some serious side effects, such as skin dryness, risks to pregnant individuals, and, in certain less-common situations, night blindness and muscle or joint pain.
Since Cutibacterium acnes is a regular denizen of the skin microbiome, and other studies have found that different strains may have favorable, nurturing properties, Knödlseder and her colleagues tried their hand at shaping the bacteria into a possible microbiome-based therapy for acne.
To do that, the researchers used a variety of genetic engineering techniques to insert the gene for NGAL into Cutibacterium acnes’ genome. After they found the newly transformed bacteria wasn’t toxic to human skin cells, they tested whether it actually produced NGAL by mingling Cutibacterium acnes with sebocytes. Sebum production was significantly decreased, the researchers write in their paper, comparably to sebocytes exposed to Accutane.
But would the genetically engineered bacteria take to actual skin? Knödlseder and her colleagues applied their Cutibacterium acnes on the backs of mouse skin and found the bacteria thrived for a number of days with no problem.
This study is still in its early stages and requires further research, especially in human subjects. However, the researchers are hopeful that their work adds to the rapid frontier of microbiome engineering and microbiome-based therapeutics to target disease and enhance human health.
“We have developed a technology platform that opens the door to editing any bacteria to treat multiple diseases,” Marc Güell, a research professor at the Universitat Pompeu Fabra who led the study, said in the press release. “We are now focused [on] using C. acnes to treat acne, but we can deliver genetic circuits to create smart microbes for applications related to skin sensing or immune modulation.”
