YSM Issue 96.2

FOCUS
Dermatology
Potential Antimicrobial Properties
Using cryo-EM, the researchers
managed to capture the first highresolution
structure of the C. acnes
ribosome. They also examined the
ribosomal proteins attached to the
ribosomal RNA and explored how the C.
acnes ribosome’s catalytic mechanisms
could differ from other known bacterial
models. This knowledge would help
inform the future design of antibiotics
against C. acnes.
But of particular interest to the team
were the bacterial small ribosomal subunit
protein 22 (bS22) and the bacterial large
ribosomal subunit protein 37 (bL37).
These proteins are normally part of the
ribosome and help synthesize proteins,
but independent of the complex, they have
displayed antimicrobial properties. C.
acnes exists in normal skin, so researchers
wonder if it helps defend the skin against
other pathogenic bacteria. “From a
dermatology perspective, we know C. acnes
lives in our follicles and pilosebaceous units
as a commensal organism—only certain
strains of it are pathogenic for acne. We
are trying to probe whether or not C. acnes
has a natural defense mechanism against
Staphylococcus aureus, which is a major
pathogenic skin organism,” Bunick said.
They discovered that the bS22 could inhibit
the growth of E. coli and S. aureus while the
bL37 only affected S. aureus but not E. coli.
The next step down the antimicrobial
properties path was to understand whether
these proteins were present independent
of the ribosome. Usually, ribosomal
proteins form a complex with ribosomal
RNAs to catalyze protein synthesis, but
additional functions outside of ribosomes
are possible. Bunick proposes that C. acnes
may either secrete these peptides directly
or release them when they die and lose
their membranes.
Sarecycline: The Better Acne-Biotic?
Sarecycline was introduced in 2018 as a
drug with higher specificity and fewer side
effects than minocycline and doxycycline.
However, primarily due to pricing issues,
it only has about six percent of the
prescription market for oral tetracycline
in dermatology. To Bunick, sarecycline
deserves more recognition. “At least to my
knowledge, it is the only FDA-approved
PHOTOGRAPHY BY EMILY POAG
Dr. Christopher Bunick (left) and Dr. Ivan Lomakin (right) discussing a model of the ribosome.
drug that targets two active centers of the
ribosomes currently,” he said.
The human gastrointestinal tract
contains many beneficial Gram-negative
bacteria. Since sarecycline is more specific
to certain Gram-positive bacteria and
spares Gram-negative bacteria, it causes
fewer side effects in the gastrointestinal tract
while effectively targeting Gram-positive
C. acnes. Doxycycline is photosensitive,
so certain users may experience rashes,
itching, or severe sunburn, while
sarecycline is not. Sarecycline is also
less hydrophobic, meaning a decreased
possibility of diffusing through the bloodbrain
barrier and causing dizziness, vertigo,
or tubular disturbance.
The Bunick lab partners with Almirall, the
pharmaceutical company that licenses and
ABOUT THE AUTHOR
sells sarecycline in the United States. “Our
laboratory [work] has been predominantly
keratins, intermediate filaments, and the
skin barrier for over a decade. But [learning
about sarecycline] presented a unique
opportunity as an entryway into a new area
of research understanding the molecular
mechanisms of dermatology drugs.
Sometimes the science leads you to where
you need to be,” Bunick said. He does
not rule out the possibility of developing
a fourth-generation tetracycline. This
paper was the first to publish a C. acnes
ribosomal structure. Given the new
information about multiple active sites, it is
possible to further optimize the structure
of the antibiotic to achieve more precise
treatment of the infection behind your
bumps and whiteheads. ■
CRYSTAL LIU
CRYSTAL LIU is a sophomore at Pierson College majoring in molecular, cellular and developmental
biology. Besides writing for YSM, she is involved in the Irish Lab, Chinese Undergraduate Students
at Yale, and Club Jump Rope. You can also find her trying out new restaurants and boba, playing
IM volleyball, and listening to a lot of Mandopop and Cantopop songs.
THE AUTHOR WOULD LIKE TO THANK Christopher Bunick and Ivan Lomakin for for their time
and enthusiasm about their research.
FURTHER READING:
Lomakin, I. B., Devarkar, S. C., Patel, S., Grada, A., & Bunick, C. G. (2023). Sarecycline inhibits
protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Nucleic
Acids Research. https://doi.org/10.1093/nar/gkad103
Batool, Z., Lomakin, I. B., Polikanov, Y. S., & Bunick, C. G. (2020). Sarecycline interferes with tRNA
accommodation and tethers mRNA to the 70s ribosome. Proceedings of the National Academy of
Sciences, 117(34), 20530–20537. https://doi.org/10.1073/pnas.2008671117
Grada, A., Del Rosso, J. Q., Moore, A. Y., Stein Gold, L., Harper, J., Damiani, G., Shaw, K., Obagi, S.,
Salem, R. J., Tanaka, S. K., & Bunick, C. G. (2022). Reduced blood-brain barrier penetration of acne
vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity.
Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.1033980
18 Yale Scientific Magazine May 2023 www.yalescientific.org