Discovery of GuaB inhibitors with efficacy against <i>Acinetobacter baumannii</i> infection
The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of <i>de novo</i> guanine biosynthesis is bactericidal in a mouse model of <i>Acinetobacter baumannii</i> infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.
Authors
- Man‐Wah Tan (ORCID: https://orcid.org/0000-0002-7748-212X)
- Terry D. Crawford (ORCID: https://orcid.org/0000-0003-4663-4116)
- Liuxi Chen (ORCID: https://orcid.org/0000-0003-1803-8835)
- Hua Zhang (ORCID: https://orcid.org/0000-0001-5936-7876)
- Eric M. Kofoed (ORCID: https://orcid.org/0000-0002-1779-4914)
- Elizabeth Skippington
- Chun Sing Li
- Chun‐Wan Yen
- Matt Baumgardner
- Janina Reeder (ORCID: https://orcid.org/0000-0002-6704-6754)
- Seth F. Harris (ORCID: https://orcid.org/0000-0003-1728-9771)
- Nicholas J. Skelton (ORCID: https://orcid.org/0009-0004-4024-3805)
- Zhengyin Yan (ORCID: https://orcid.org/0000-0002-8086-5615)
- Yiming Xu (ORCID: https://orcid.org/0000-0002-8866-7859)
- Summer Park
- Savita Ubhayakar (ORCID: https://orcid.org/0000-0002-4354-4855)
- Ying Yang (ORCID: https://orcid.org/0000-0002-4810-2976)
- Xiaorong Liang (ORCID: https://orcid.org/0000-0002-2428-5579)
- Fang Ma (ORCID: https://orcid.org/0000-0002-0017-8373)
- Zhiguo Liu (ORCID: https://orcid.org/0000-0002-8485-7356)
- Ping Wu (ORCID: https://orcid.org/0000-0003-2650-9043)
- Jun Liang (ORCID: https://orcid.org/0000-0001-5318-4323)
- Xingrong Liu (ORCID: https://orcid.org/0000-0002-0749-1469)
- Jialin Mao (ORCID: https://orcid.org/0000-0001-8635-7454)
- Min Xu (ORCID: https://orcid.org/0000-0001-8554-2439)
- Shumei Wang (ORCID: https://orcid.org/0000-0001-6649-3117)
- Yutian Peng (ORCID: https://orcid.org/0000-0002-8663-7330)
- Jacob Chen (ORCID: https://orcid.org/0000-0002-4047-8071)
- María Lorenzo
- Kevin Clark (ORCID: https://orcid.org/0000-0001-6660-0736)
- Bridget Hoag
- Ignacio Aliagas
- John Wai
- Jessica Sims
Institutions
- WuXi AppTec (China) (CN)
Publication Details
- Journal
- mBio
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1128/mbio.00897-24
- Citations
- 8
- Primary Topic
- Biochemical and Molecular Research
- Type
- article
- Field-Weighted Citation Impact
- 1.87