mBio (Feb 2021)
Predictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosa
- Jitender Mehla,
- Giuliano Malloci,
- Rachael Mansbach,
- Cesar A. López,
- Ruslan Tsivkovski,
- Keith Haynes,
- Inga V. Leus,
- Sally B. Grindstaff,
- Robert H. Cascella,
- Napoleon D’Cunha,
- Liam Herndon,
- Nicolas W. Hengartner,
- Enrico Margiotta,
- Alessio Atzori,
- Attilio V. Vargiu,
- Pedro D. Manrique,
- John K. Walker,
- Olga Lomovskaya,
- Paolo Ruggerone,
- S. Gnanakaran,
- Valentin V. Rybenkov,
- Helen I. Zgurskaya
Affiliations
- Jitender Mehla
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- Giuliano Malloci
- ORCiD
- Department of Physics, University of Cagliari, Cagliari, Italy
- Rachael Mansbach
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
- Cesar A. López
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
- Ruslan Tsivkovski
- Qpex Biopharma, San Diego, California, USA
- Keith Haynes
- Department of Pharmacology and Physiology, St. Louis University, School of Medicine, St. Louis, Missouri, USA
- Inga V. Leus
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- Sally B. Grindstaff
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- Robert H. Cascella
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- Napoleon D’Cunha
- Department of Pharmacology and Physiology, St. Louis University, School of Medicine, St. Louis, Missouri, USA
- Liam Herndon
- Department of Pharmacology and Physiology, St. Louis University, School of Medicine, St. Louis, Missouri, USA
- Nicolas W. Hengartner
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
- Enrico Margiotta
- Department of Physics, University of Cagliari, Cagliari, Italy
- Alessio Atzori
- Department of Physics, University of Cagliari, Cagliari, Italy
- Attilio V. Vargiu
- ORCiD
- Department of Physics, University of Cagliari, Cagliari, Italy
- Pedro D. Manrique
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
- John K. Walker
- Department of Pharmacology and Physiology, St. Louis University, School of Medicine, St. Louis, Missouri, USA
- Olga Lomovskaya
- ORCiD
- Qpex Biopharma, San Diego, California, USA
- Paolo Ruggerone
- ORCiD
- Department of Physics, University of Cagliari, Cagliari, Italy
- S. Gnanakaran
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
- Valentin V. Rybenkov
- ORCiD
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- Helen I. Zgurskaya
- ORCiD
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- DOI
- https://doi.org/10.1128/mBio.02785-20
- Journal volume & issue
-
Vol. 12,
no. 1
Abstract
Efflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular and physicochemical interactions defining the interface between compounds and efflux pumps remain poorly understood. We identified properties that correlate with efflux avoidance and inhibition, are predictive of similar features in structurally diverse compounds, and allow researchers to distinguish between efflux substrates, inhibitors, and avoiders in P. aeruginosa
