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Review
. 2020 Feb 7;9(2):69.
doi: 10.3390/antibiotics9020069.

Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ

Andrea Casiraghi  1 , Lorenzo Suigo  1 , Ermanno Valoti  1 , Valentina Straniero  1
Affiliations
Review

Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ

Andrea Casiraghi et al. Antibiotics (Basel). .

Abstract

Binary fission is the most common mode of bacterial cell division and is mediated by a multiprotein complex denominated the divisome. The constriction of the Z-ring splits the mother bacterial cell into two daughter cells of the same size. The Z-ring is formed by the polymerization of FtsZ, a bacterial protein homologue of eukaryotic tubulin, and it represents the first step of bacterial cytokinesis. The high grade of conservation of FtsZ in most prokaryotic organisms and its relevance in orchestrating the whole division system make this protein a fascinating target in antibiotic research. Indeed, FtsZ inhibition results in the complete blockage of the division system and, consequently, in a bacteriostatic or a bactericidal effect. Since many papers and reviews already discussed the physiology of FtsZ and its auxiliary proteins, as well as the molecular mechanisms in which they are involved, here, we focus on the discussion of the most compelling FtsZ inhibitors, classified by their main protein binding sites and following a medicinal chemistry approach.

Keywords: FtsZ inhibitors; GTP-binding site; bacterial cell division process; interdomain site.

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Conflict of interest statement

The authors declare no conflict of interest

Figures

Figure 1
Figure 1
Graphical representation of FtsZ main subunits and sequence alignment of FtsZ from representative organisms: Staphylococcus aureus (Sau), Bacillus subtilis (Bsu), Escherichia coli (Eco), and Pseudomonas aeruginosa (Pae). Alignments: * = same residues, : = equivalent residues, · = partial alignment. The sequences were obtained from uniport.org (identifiers (IDs): P0A031, P17865, P0A9A6, P47204) and aligned with EMBL-EBI Clustal Omega (www.ebi.ac.uk/Tools/msa/clustalo/).
Figure 2
Figure 2
Flowchart of the main steps in FtsZ inhibition confirmation.
Figure 3
Figure 3
Pyrimidine FtsZ inhibitors.
Figure 4
Figure 4
Zantrin FtsZ inhibitors.
Figure 5
Figure 5
Chrysophaentin FtsZ inhibitors.
Figure 6
Figure 6
GTP analogues and derived synthetic FtsZ inhibitors.
Figure 7
Figure 7
Benzamide inhibitors.
Figure 8
Figure 8
Berberine-based inhibitors.
Figure 9
Figure 9
Phenantridium inhibitors.
Figure 10
Figure 10
Tiplaxtinin.
See this image and copyright information in PMC

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