Inhibitors of bacterial tubulin target bacterial membranes in vivo

Marie H. Foss, Ye Jin Eun, Charles I. Grove, Daniel A. Pauw, Nohemy A. Sorto, Jarred W. Rensvold, David J. Pagliarini, Jared T. Shaw, Douglas B. Weibel

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

FtsZ is a homolog of eukaryotic tubulin that is widely conserved among bacteria and coordinates the assembly of the cell division machinery. FtsZ plays a central role in cell replication and is a target of interest for antibiotic development. Several FtsZ inhibitors have been reported. We characterized the mechanism of these compounds in bacteria and found that many of them disrupt the localization of membrane-associated proteins, including FtsZ, by reducing the transmembrane potential or perturbing membrane permeability. We tested whether the reported phenotypes of a broad collection of FtsZ inhibitors disrupt the transmembrane potential in Bacillus subtilis strain 168. Using a combination of flow cytometry and microscopy, we found that zantrin Z1, cinnamaldehyde, totarol, sanguinarine, and viriditoxin decreased the B. subtilis transmembrane potential or perturbed membrane permeability, and influenced the localization of the membrane-associated, division protein MinD. These studies demonstrate that small molecules that disrupt membrane function in bacterial cells produce phenotypes that are similar to the inhibition of proteins associated with membranes in vivo, including bacterial cytoskeleton homologs, such as FtsZ. The results provide a new dimension for consideration in the design and testing of inhibitors of bacterial targets that are membrane-associated and provide additional insight into the structural characteristics of antibiotics that disrupt the membrane. This journal is

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalMedChemComm
Volume4
Issue number1
DOIs
StatePublished - Jan 2013

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Tubulin Modulators
Tubulin
Membranes
Membrane Potentials
Membrane Proteins
Bacillus subtilis
Permeability
Anti-Bacterial Agents
Bacteria
Phenotype
Cytoskeleton
Cell Division
Microscopy
Flow cytometry
Flow Cytometry
Bacilli
Machinery
Microscopic examination
Proteins
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Cite this

Foss, M. H., Eun, Y. J., Grove, C. I., Pauw, D. A., Sorto, N. A., Rensvold, J. W., ... Weibel, D. B. (2013). Inhibitors of bacterial tubulin target bacterial membranes in vivo. MedChemComm, 4(1), 112-119. https://doi.org/10.1039/c2md20127e

Inhibitors of bacterial tubulin target bacterial membranes in vivo. / Foss, Marie H.; Eun, Ye Jin; Grove, Charles I.; Pauw, Daniel A.; Sorto, Nohemy A.; Rensvold, Jarred W.; Pagliarini, David J.; Shaw, Jared T.; Weibel, Douglas B.

In: MedChemComm, Vol. 4, No. 1, 01.2013, p. 112-119.

Research output: Contribution to journalArticle

Foss, MH, Eun, YJ, Grove, CI, Pauw, DA, Sorto, NA, Rensvold, JW, Pagliarini, DJ, Shaw, JT & Weibel, DB 2013, 'Inhibitors of bacterial tubulin target bacterial membranes in vivo', MedChemComm, vol. 4, no. 1, pp. 112-119. https://doi.org/10.1039/c2md20127e
Foss MH, Eun YJ, Grove CI, Pauw DA, Sorto NA, Rensvold JW et al. Inhibitors of bacterial tubulin target bacterial membranes in vivo. MedChemComm. 2013 Jan;4(1):112-119. https://doi.org/10.1039/c2md20127e
Foss, Marie H. ; Eun, Ye Jin ; Grove, Charles I. ; Pauw, Daniel A. ; Sorto, Nohemy A. ; Rensvold, Jarred W. ; Pagliarini, David J. ; Shaw, Jared T. ; Weibel, Douglas B. / Inhibitors of bacterial tubulin target bacterial membranes in vivo. In: MedChemComm. 2013 ; Vol. 4, No. 1. pp. 112-119.
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