Potentiation of Antibiotics against Gram-Negative Bacteria by Polymyxin B Analogue SPR741 from Unique Perturbation of the Outer Membrane

Shawn French, Maya A. Farha, Michael J. Ellis, Zaid Sameer, Jean‐Philippe Côté, Nicole Cotroneo, Troy Lister, Aileen Rubio, Eric D. Brown

ACS Infectious Diseases · 2019 · 107 citations · 32 references

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Concepts

Abstract

to SPR741, suggesting that LPS core residues keep SPR741 at the OM, where it can potentiate a codrug, rather than permit its entry to the cytoplasmic membrane. Further, a promoter activity assay revealed that SPR741 challenge induced the expression of RcsAB, a stress sensor for OM perturbation. Together, these results indicate that SPR741 interacts predominately with the OM, in contrast to the dual action of PMB and colistin at both the outer and cytoplasmic membranes.

References

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