Publication: Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus
Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus
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Phelps, G. A., Cheramie, M. N., Fernando, D. M., Selchow, P., Meyer, C. J., Waidyarachchi, S. L., Dharuman, S., Liu, J., Meuli, M., Molin, M. D., Killam, B. Y., Murphy, P. A., Reeve, S. M., Wilt, L. A., Anderson, S. M., Yang, L., Lee, R. B., Temrikar, Z. H., Lukka, P. B., … Lee, R. E. (2024). Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus. Proceedings of the National Academy of Sciences of the United States of America, 121, e2314101120. https://doi.org/10.1073/pnas.2314101120
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Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography stu
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Phelps, G. A., Cheramie, M. N., Fernando, D. M., Selchow, P., Meyer, C. J., Waidyarachchi, S. L., Dharuman, S., Liu, J., Meuli, M., Molin, M. D., Killam, B. Y., Murphy, P. A., Reeve, S. M., Wilt, L. A., Anderson, S. M., Yang, L., Lee, R. B., Temrikar, Z. H., Lukka, P. B., … Lee, R. E. (2024). Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus. Proceedings of the National Academy of Sciences of the United States of America, 121, e2314101120. https://doi.org/10.1073/pnas.2314101120
