Antisense peptide nucleic acids againstftsZ andefaA genes inhibit growth and biofilm formation of Enterococcus faecalis

Narenji, Hanar; Teymournejad, Omid; Rezaee, Mohammad Ahangarzadeh; Taghizadeh, Sepehr; Mehramuz, Bahareh; Aghazadeh, Mohammad; Asgharzadeh, Mohammad; Madhi, Masoumeh; Gholizadeh, Pourya; Ganbarov, Khudaverdi; Yousefi, Mehdi; Pakravan, Asrin; Dal, Tuba; Ahmadi, Raman; Kafil, Hossein Samadi

doi:10.1016/j.micpath.2019.103907

Cited by 34 publications

(26 citation statements)

References 43 publications

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“…The surface protein of E. faecalis (encrypted by chromosomal Esp) is involved in the primary binding and biofilm formation of this bacterium, and with the exacerbation of the disease, colonization is accompanied by bacterial sta- bility in host tissues, especially in the urinary tract (18). Therefore, inhibiting biofilm formation is medically important (19). In this study, the in vitro and in silico ability of newly synthesized derivatives to inhibit biofilm formation induced by Esp was investigated.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Silico Evaluation of Biological Activity of a New Series of Oxadiazole Compounds Against Esp Gene Expression in Enterococcus faecalis Biofilm

2021

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Background: The enterococcal surface protein (Esp) is a high-molecular-weight surface protein of biofilm creating agent in Enterococcus faecalis. Oxadiazoles have a wide range of biological activities. Objective: This research aimed to examine the impact of new oxadiazole derivatives on the expression of Esp, playing an important role in promoting the biofilm formation ability of drug-resistant E. faecalis strains. Method: 1, 3, 4-oxadiazole derivatives were synthesized through a one-step synthesis. E. faecalis strains were collected and isolated from hospitals in Tehran. The antimicrobial properties of the synthesized materials against the isolated strains were investigated. RNA, DNA, and cDNA were extracted, and the relative expression of Esp in E. faecalis isolates was evaluated by real-time PCR. Docking study was performed by AutoDock vina software, and the resulting docking poses were analyzed using Discovery Studio 4.5 Client software. Results: The use of synthesized derivatives changed the Esp expression level in different isolates compared to the control sample. The two compounds containing naphthalene (4f) and methoxyphenyl (4g) caused respectively a 2-fold and a 3-fold decrease in Esp expression compared to the control sample. The compound 4f with the best binding energy among the compounds (-9.2) had the most hydrogen and hydrophobic bonds with the receptor-binding site. Conclusions: 1, 3, 4-oxadiazole derivatives, especially naphthalene and methoxyphenyl, act as inhibitors of bacterial biofilm formation and can be used in the pharmaceutical and biological industries.

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Section: Discussionmentioning

confidence: 99%

In Vitro and In Silico Evaluation of Biological Activity of a New Series of Oxadiazole Compounds Against Esp Gene Expression in Enterococcus faecalis Biofilm

2021

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“…Liang et al designed (RXR) 4 XB‐conjugated PNAs targeting FtsZ, including PPNA1 (targeting 309–323 nucleotides of ftsZ gene) and PPNA2 (targeting the translation initiation and ribosomal‐binding sites of ftsZ ), could inhibit the growth of MRSA in vitro by the downregulation of ftsZ gene expression in a dose‐dependent manner [75]. Narenji et al conjugated (RXR) 4 XB‐PNA targeting ftsZ and efaA genes of Enterococcus faecalis , which involves in biofilm formation and cell division, respectively [77]. The results showed that this conjugate inhibited cell division, cell growth, and biofilm formation of E. faecalis .…”

Section: Structure and Function Of Ftszmentioning

confidence: 99%

“…The results showed that this conjugate inhibited cell division, cell growth, and biofilm formation of E. faecalis . Moreover, the peptide‐PNA had no cytotoxicity toward MCF7 cells [77].…”

Section: Structure and Function Of Ftszmentioning

confidence: 99%

Recent progress of bacterial FtsZ inhibitors with a focus on peptides

Han

Wang

et al. 2020

The FEBS Journal

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In recent years, the rise of antibiotic resistance has become a primary health problem. With the emergence of bacterial resistance, the need to explore and develop novel antibacterial drugs has become increasingly urgent. Filamentous temperature-sensitive mutant Z (FtsZ), a crucial cell division protein of bacteria, has become a vital antibacterial target. FtsZ is a filamentous GTPase; it is highly conserved in bacteria and shares less than 20% sequence identity with the eukaryotic cytoskeleton protein tubulin, indicating that FtsZ-targeting antibacterial agents may have a low cytotoxicity toward eukaryotes. FtsZ can form a dynamic Z-ring in the center of the cell resulting in cell division. Furthermore, disturbance in the assembly of FtsZ may affect cellular dynamics and bacterial cell survival, making it a fascinating target for drug development. This review focuses on the recent discovery of FtsZ inhibitors, including peptides, natural products, and other synthetic small molecules, as well as their mechanism of action, which could facilitate the discovery of novel FtsZ-targeting clinical drugs in the future.

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“…Moreover, the pace of emerging antibiotic resistance far exceeds the pace of development of new antibiotics, which is insufficient to combat the rise in antibiotic resistance. 7 Therefore, new approaches have been suggested for decreasing and limiting antibiotic resistance in pathogens, including phage therapy, 2,8,9 use of peptide nucleic acid (PNA) as an ultra-narrow-spectrum antibiotic, 6,10,14 zinc finger nucleases (ZFNs), 15,16 and clustered regularly interspaced short palindromic repeat -CRISPR-associated (CRISPR-Cas) systems, 5,17,19 which are genomic engineering tools for gene knock-out and knock-in of sequence-specific DNA antibiotic targets. Bacteriophages are bacteria-specific viruses, which can specifically infect and lyse bacteria.…”

Section: Introductionmentioning

confidence: 99%

<p>How CRISPR-Cas System Could Be Used to Combat Antimicrobial Resistance</p>

Gholizadeh¹,

Köse²,

Dao³

et al. 2020

IDR

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Rapid emergence of antibiotic-resistant bacteria has made it harder for us to combat infectious diseases and to develop new antibiotics. The clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) system, as a bacterial adaptive immune system, is recognized as one of the new strategies for controlling antibioticresistant strains. The programmable Cas nuclease of this system used against bacterial genomic sequences could be lethal or could help reduce resistance of bacteria to antibiotics. Therefore, this study aims to review using the CRISPR-Cas system to promote sensitizing bacteria to antibiotics. We envision that CRISPR-Cas approaches may open novel ways for the development of smart antibiotics, which could eliminate multidrug-resistant (MDR) pathogens and differentiate between beneficial and pathogenic microorganisms. These systems can be exploited to quantitatively and selectively eliminate individual bacterial strains based on a sequence-specific manner, creating opportunities in the treatment of MDR infections, the study of microbial consortia, and the control of industrial fermentation.

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Antisense peptide nucleic acids againstftsZ andefaA genes inhibit growth and biofilm formation of Enterococcus faecalis

Cited by 34 publications

References 43 publications

In Vitro and In Silico Evaluation of Biological Activity of a New Series of Oxadiazole Compounds Against Esp Gene Expression in Enterococcus faecalis Biofilm

In Vitro and In Silico Evaluation of Biological Activity of a New Series of Oxadiazole Compounds Against Esp Gene Expression in Enterococcus faecalis Biofilm

Recent progress of bacterial FtsZ inhibitors with a focus on peptides

<p>How CRISPR-Cas System Could Be Used to Combat Antimicrobial Resistance</p>

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