A new study has identified how the third-generation tetracycline antibiotic sarecycline has a strong specificity for C. acnes while also seeming to have a low risk of encouraging antibiotic resistance.
Published in Nucleic Acids Research, the study describes how researchers visualized the C. acnes ribosome and how sarecycline interacts with it.
“This is a huge step in the right direction towards pathogen-specific antibiotic development,” said the study’s principal investigator Christopher Bunick, MD, PhD, in a press release. “If we can understand sarecycline’s low propensity for antibiotic resistance in C. acnes, that allows for the future development of even more targeted and safer antibiotics or other medicines with minimal resistance risk.”
Dr. Bunick is an associate professor of dermatology at the Yale School of Medicine in New Haven, Conn.
The investigation revealed that, unlike other antibiotics, sarecycline is bound to not one, but two active sites on the ribosome. Earlier studies of sarecycline in the model ribosome of the bacteria Thermus thermophilus found only one binding site.
The authors write that the second binding site is similar to one that interacts with the macrolides class of antibiotics.
According to the release, these findings are important for two reasons. First, this is the first group to visualize the structure of the C. acnes ribosome itself and make several observations. C. acnes ribosomes have proteins with zinc-free and zinc-bound isoforms. Some dermatology research suggests that zinc supplementation might help treat acne vulgaris and support antibiotic treatments. This work further supports that zinc supplementation may be helpful in treating acne.
Second, the model explains why sarecycline use is less likely to lead to antibiotic-resistant mutations.
“The probability of having a mutation at one ribosomal site is high, but the probability of having mutations at two sites at the same time is much lower,” said the paper’s lead author Ivan Lomakin, PhD, an associate research scientist in dermatology at Yale.