Characterizing the response of Acinetobacter baumannii ATCC 17978 to azithromycin in multiple in vitro growth conditions

Dillon, N. A.; Seif, Y.; Tsunemoto, H.; Poudel, S.; Meehan, M.; Szubin, R.; Olson, C.; Rajput, A.; Alarcon, G.; Lamsa, A.; Vrbanac, A.; Sugie, J.; Dahesh, S.; Monk, J.; Dorrestein, P.; Knight, R.; Feist, A.; Pogliano, J.; Palsson, B.; Nizet, V.

doi:10.1101/2020.05.19.079962

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bioRxiv · 10.1101/2020.05.19.079962

Characterizing the response of Acinetobacter baumannii ATCC 17978 to azithromycin in multiple in vitro growth conditions

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Abstract

Multi-drug resistant (MDR) Acinetobacter baumannii is one of the most concerning pathogens in hospital infections. A. baumannii is categorized as an "Urgent Threat" by the U.S. Centers for Disease Control and the highest priority pathogen by the World Health Organization due to its propensity for broad antibiotic resistance and its associated high mortality rates. New treatment options are urgently needed for MDR A. baumannii infections. Our prior studies have demonstrated an unappreciated utility of the macrolide azithromycin (AZM) against MDR A. baumannii in tissue-culture medium. This finding is all the more surprising since AZM has no appreciable activity against A. baumannii in standard bacteriological media. The basis for this media-dependent activity of AZM against A. baumannii is not fully defined. In this study, we utilize a variety of techniques (growth dynamics, bacterial cytological profiling, RNA sequencing, and LC/MS) to profile the response of MDR A. baumannii to AZM in both standard bacteriological and more physiological relevant mammalian tissue-culture medium. [Table 1]

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Dillon, N. A., Seif, Y., Tsunemoto, H., Poudel, S., Meehan, M., Szubin, R., Olson, C., Rajput, A., Alarcon, G., Lamsa, A., Vrbanac, A., Sugie, J., Dahesh, S., Monk, J., Dorrestein, P., Knight, R., Feist, A., Pogliano, J., Palsson, B., Nizet, V.. 2020-05-20. Characterizing the response of Acinetobacter baumannii ATCC 17978 to azithromycin in multiple in vitro growth conditions. https://doi.org/10.1101/2020.05.19.079962

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