Recent progress of bacterial FtsZ inhibitors with a focus on peptides

Han, Huihui; Wang, Zhenlong; Li, Ting; Teng, Da; Mao, Ruoyu; Hao, Ya; Yang, Na; Wang, Xiumin; Wang, Jianhua

doi:10.1111/febs.15489

Cited by 40 publications

(16 citation statements)

References 136 publications

(208 reference statements)

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“…Cell division is a critical process for microbial survival. Among the proteins involved in this process, FtsZ has a pivotal function in which it serves as a scaffold for the assembly of a multiprotein complex structure, the divisome, responsible for coordinating all the steps of cell division and cell wall remodeling 16 . The protein acts during cell division as an organizer of the cytoplasmic ring in bacteria and can be considered the main target of several bactericidal compounds 17 .…”

Section: Introductionmentioning

confidence: 99%

Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens

Mendes

Dilarri

Forsan

et al. 2022

Sci Rep

284

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Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanoparticulate materials due to their antimicrobial properties, but their main mechanism of action (MOA) has not been fully elucidated. This study characterized ZnO NPs by using X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy. Antimicrobial activity of ZnO NPs against the clinically relevant bacteria Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and the Gram-positive model Bacillus subtilis was evaluated by performing resazurin microtiter assay (REMA) after exposure to the ZnO NPs at concentrations ranging from 0.2 to 1.4 mM. Sensitivity was observed at 0.6 mM for the Gram-negative and 1.0 mM for the Gram-positive cells. Fluorescence microscopy was used to examine the interference of ZnO NPs on the membrane and the cell division apparatus of B. subtilis (amy::pspac-ftsZ-gfpmut1) expressing FtsZ-GFP. The results showed that ZnO NPs did not interfere with the assembly of the divisional Z-ring. However, 70% of the cells exhibited damage in the cytoplasmic membrane after 15 min of exposure to the ZnO NPs. Electrostatic forces, production of Zn2+ ions and the generation of reactive oxygen species were described as possible pathways of the bactericidal action of ZnO. Therefore, understanding the bactericidal MOA of ZnO NPs can potentially help in the construction of predictive models to fight bacterial resistance.

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Section: Introductionmentioning

confidence: 99%

Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens

Mendes

Dilarri

Forsan

et al. 2022

Sci Rep

284

View full text Add to dashboard Cite

show abstract

“…Cell division is a critical process for microbial survival. Among the proteins involved in this process, FtsZ has a pivotal function in which it serves as a scaffold for the assembly of a multiprotein complex structure, the divisome, responsible for coordinating all the steps of cell division and cell wall remodeling [15]. The protein acts during cell division as an organizer of the cytoplasmic ring in bacteria and can be considered the main target of several bactericidal compounds [16].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Action and Target Mechanisms of Zinc Oxide Nanoparticles Against Bacterial Pathogens

Mendes

Dilarri

Forsan

et al. 2021

Preprint

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Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanoparticulate materials due to their antimicrobial properties, but their main mechanism of action (MOA) has not been fully elucidated. The study characterized ZnO NPs using X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy. Antimicrobial activity of clinically bacteria Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa was evaluated by REMA after exposure to the ZnO NP at concentrations from 0.2 to 1.4 mM. Sensitivity was achieved at 0.6 mM for the Gram-negatives and 1.0 mM for Gram-positives cells. The effect of ZnO NPs on the membrane integrity and in the interference of cell division was investigated by its effect on the divisional ring, through fluorescence microscopy assays using B. subtilis (amy::pspac-ftsZ-gfpmut1) expressing FtsZ-GFP. Results showed that ZnO NPs did not interfere with the assembly of the divisional Z-ring. However, 70% of the cells showed damage in the cytoplasmic membrane after 15 min of exposure to the ZnO NPs. Electrostatic forces, production of Zn2+ ions, generation of reactive oxygen species were described as pathways of bactericidal action by ZnO. Thus, understanding bactericidal MOA can produce predictive models to prevent bacterial resistance and lead to further research.

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“…Nowadays, Ftsz is recognized as a leading target in the search for new antibacterial compounds, since it is an essential protein for cell division in most bacteria and is absent in humans [16]. A large number of FtsZ inhibitors, including peptides, natural products, and other synthetic small molecules, have been proposed which might lead to the discovery of novel FtsZ-targeting clinical drugs [17].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Temporin-L Analogues with the E. coli FtsZ Protein

et al. 2021

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The research of new therapeutic agents to fight bacterial infections has recently focused on the investigation of antimicrobial peptides (AMPs), the most common weapon that all organisms produce to prevent invasion by external pathogens. Among AMPs, the amphibian Temporins constitute a well-known family with high antibacterial properties against Gram-positive and Gram-negative bacteria. In particular, Temporin-L was shown to affect bacterial cell division by inhibiting FtsZ, a tubulin-like protein involved in the crucial step of Z-ring formation at the beginning of the division process. As FtsZ represents a leading target for new antibacterial compounds, in this paper we investigated in detail the interaction of Temporin L with Escherichia coli FtsZ and designed two TL analogues in an attempt to increase peptide-protein interactions and to better understand the structural determinants leading to FtsZ inhibition. The results demonstrated that the TL analogues improved their binding to FtsZ, originating stable protein-peptide complexes. Functional studies showed that both peptides were endowed with a high capability of inhibiting both the enzymatic and polymerization activities of the protein. Moreover, the TL analogues were able to inhibit bacterial growth at low micromolar concentrations. These observations may open up the way to the development of novel peptide or peptidomimetic drugs tailored to bind FtsZ, hampering a crucial process of bacterial life that might be proposed for future pharmaceutical applications.

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Recent progress of bacterial FtsZ inhibitors with a focus on peptides

Cited by 40 publications

References 136 publications

Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens

Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens

Antibacterial Action and Target Mechanisms of Zinc Oxide Nanoparticles Against Bacterial Pathogens

Interaction of Temporin-L Analogues with the E. coli FtsZ Protein

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